The Reds will be buoyed by their victory over United in the FA Cup last month, while the game is likely to see Luis Suarez and Patrice Evra lock horns for the first time since the Uruguayan was slapped with an eight-match ban for racially abusing the latter.
Arsenal face a tough test when they travel to the Stadium of Light to play in-form Sunderland, while Chelsea face a tricky trip to Everton.
Two of the season's surprise outfits face off at White Hart Lane when Tottenham host Newcastle, while league leaders Manchester City are in action on when they travel to Aston Villa.
Ahead of this weekend's matches, we take a look at all the news from the selection table.
Man United vs Liverpool
Tom Cleverley is expected to play some part in Manchester United's crucial Barclays Premier League encounter with Liverpool at Old Trafford on Saturday.
Cleverley has been out since October with an ankle injury but has now recovered and is likely to be on the bench.
Chris Smalling (knock) is set to return but Phil Jones (ankle) is still missing.
Liverpool striker Luis Suarez is set to face United for the first time since being banned for eight matches for racially abusing Patrice Evra.
The Uruguay international looked sharp on his comeback in a 24-minute substitute appearance in the goalless draw at home to Tottenham on Monday.
Left-back Jose Enrique missed that match with a hamstring problem but is expected to be fit enough to return.
Man United (from): De Gea, Amos, Smalling, Rafael, Ferdinand, Evra, Evans, Fabio, Fryers, Cole, Carrick, Cleverley, Scholes, Pogba, M Keane, Valencia, Park, Giggs, Young, Nani, Rooney, Welbeck, Berbatov, Hernandez.
Liverpool (from): Reina, Johnson, Agger, Skrtel, Enrique, Adam, Gerrard, Downing, Kuyt, Carroll, Bellamy, Suarez, Doni, Kelly, Carragher, Coates, Aurelio, Spearing, Shelvey, Henderson, Rodriguez.
Everton vs Chelsea
Midfielders Frank Lampard (calf) and John Obi Mikel (hamstring) are in contention to return for Chelsea at Everton.
Full-back Ashley Cole served a suspension against Manchester United last weekend, but captain John Terry is still not fit from a knee problem.
Brazilian midfielder Ramires (knee) also remains sidelined.
Everton midfielder Jack Rodwell has suffered a minor setback in his recovery from a hamstring problem and will not be risked.
The 20-year-old has struggled with the injury since November and has made only three appearances since then, the last coming a month ago.
Phil Jagielka, Leon Osman (both knee) and Seamus Coleman (thigh) are still unavailable.
Everton (from): Howard, Heitinga, Baines, Hibbert, Distin, Neville, Gibson, Cahill, Drenthe, Fellaini, Donovan, Stracqualursi, Mucha, Duffy, Gueye, Vellios, Pienaar, Jelavic, McFadden.
Chelsea (from): Cech, Bosingwa, Cahill, Ivanovic, Luiz, Malouda, Meireles, Essien, Torres, Sturridge, Romeu, Mata, Piazon, Lukaku, Hutchinson, Turnbull, Bertrand, Ferreira, Lampard, Mikel.
Sunderland vs Arsenal
Loan signings Wayne Bridge and Sotirios Kyrgiakos return to the Sunderland squad for Saturday's Barclays Premier League clash with Arsenal.
The former England full-back and the Greece central defender were ineligible for Wednesday's FA Cup fourth round replay victory at Middlesbrough having not arrived on Wearside in time to be registered, although striker Nicklas Bendtner cannot play against his parent club under the terms of his loan agreement.
Defender Matt Kilgallon has returned to training after an ankle injury, but he is short of match fitness after five games on the sidelines, while Lee Cattermole (hamstring), David Vaughan (ankle), Wes Brown (knee) and Titus Bramble (Achilles/calf) are still out.
Arsenal could have defender Kieran Gibbs back in their squad after his recovery from a groin injury.
Striker Marouane Chamakh has returned from the African Nations Cup, but Gervinho remains away as Ivory Coast prepare for the final.
Defenders Carl Jenkinson (back) and Andre Santos (ankle) are still out, along with midfielders Abou Diaby (hamstring) and Jack Wilshere (ankle). Emmanuel Frimpong has returned from his loan spell at Wolves, but will be out for the rest of the season after needing surgery on his knee.
Sunderland (from): Mignolet, Westwood, Bardsley, Bridge, O'Shea, Turner, Kyrgiakos, Lynch, Richardson, Gardner, Larsson, Elmohamady, McClean, Meyler, Colback, Sessegnon, Wickham, Ji, Campbell.
Arsenal (from): Szczesny, Vermaelen, Mertesacker, Koscielny, Sagna, Walcott, Song, Benayoun, Coquelin, Oxlade-Chamberlain, Henry, Rosicky, Arteta, Van Persie, Park, Arshavin, Fabianski, Ramsey, Chamakh, Gibbs.
Swansea vs Norwich
Norwich defender Elliott Ward could be in line to make his first appearance of the season when the Canaries visit Swansea on Saturday after six months on the sidelines with a knee problem.
Centre-back Daniel Ayala will be out of action for around four weeks with a hamstring injury and partner Zak Whitbread is doubtful as he recovers from a hamstring strain.
Full-back Marc Tierney has still not recovered from a groin problem while striker James Vaughan is training well but not yet match fit.
Swansea manager Brendan Rodgers has a near full-strength squad to pick from.
Rodgers, who signed a new three-and-a-half year contract earlier this week, is likely to stick with the starting line-up that secured a 2-1 win at West Brom last weekend.
New signing Curtis Obeng is unlikely to be rushed into the squad following his recent arrival from Wrexham, while midfielder Ferrie Bodde is again on the sidelines after being hit by another knee injury and Andrea Orlandi (hamstring) is also out.
Swansea (from): Vorm, Williams, Taylor, Caulker, Tate, Britton, Graham, Sinclair, Dyer, Dobbie, Routledge, Monk, McEachran, Lita, Moore, Bessone, Rangel, Situ, Allen, Tremmel, Agustien, Gower, Richards, Sigurdsson.
Norwich (from): Ruddy, Naughton, Bennett, Martin, Whitbread Drury, Fox, Pilkington, Surman, Hoolahan, Holt, Jackson, Morison, Steer, Johnson, Crofts, Wilbraham, Ward, Lappin, Barnett.
Blackburn vs QPR
Blackburn striker Aiyegbeni Yakubu is set to make his return in Saturday's Barclays Premier League match against QPR at Ewood Park after a three-match suspension.
Defender Christopher Samba has been ruled out with a hamstring problem and Gael Givet will serve the first of a three-game ban following his sending off during the 7-1 defeat to Arsenal at Emirates Stadium last Saturday.
Midfielder Jason Lowe could be back in contention after responding well to treatment to an ankle injury he sustained against the Gunners.
Striker Djibril Cisse is one of a host of QPR first-team players that will miss the match.
The France international starts a three-match ban after his red card against Wolves last week, while Heidar Helguson (groin), DJ Campbell and Luke Young (both hamstring) also miss out.
Jay Bothroyd (groin), Akos Buzsaky (Achilles) and Danny Gabbidon (hip) could all return from injury at Ewood Park.
Blackburn (from): Robinson, Lowe, Orr, Dann, Hanley, Martin Olsson, Pedersen, Petrovic, Nzonzi, Hoilett, Dunn, Yakubu, Formica, Modeste, Goodwillie, Marcus Olsson, Rochina, Vukcevic, Henley, Slew, Blackman.
QPR (from): Kenny, Cerny, Murphy, Gabbidon, Onuoha, Ferdinand, Taiwo, Traore, Hall, Hill, Derry, Barton, Buzsaky, Taarabt, Smith, Mackie, Wright-Phillips, Hulse, Macheda, Bothroyd, Zamora.
Bolton vs Wigan
Tim Ream could finally make his debut for Bolton in Saturday's crunch Barclays Premier League game against Wigan at the Reebok Stadium.
United States centre-back Ream, whose move from the New York Red Bulls was confirmed over a fortnight ago, has started training with his new team-mates this week after all the paperwork relating to the deal was completed. He is set to be part of the Wanderers matchday squad for the first time, along with fellow January recruit Ryo Miyaichi, the Japanese winger signed on loan from Arsenal for the rest of the season.
Gretar Steinsson (hamstring) and Joe Riley (groin) may return having missed last weekend's 2-0 defeat at Norwich, but another defender Marcos Alonso (foot) is not yet ready, while midfielders Lee Chung-yong (broken leg) Stuart Holden and Ricardo Gardner (both knee) remain long-term injury absentees.
Wigan are at full strength for their crucial Barclays Premier League trip to neighbours and fellow strugglers Bolton on Saturday.
Defender Antolin Alcaraz (groin) is back in contention to start after being left on the bench against Everton last week.
Midfielder Mohamed Diame could also make his first appearance since returning from the African Nations Cup.
Bolton (from): Bogdan, Jaaskelainen, Ream, Wheater, Boyata, Knight, Steinsson, Mears, Robinson, Ricketts, Riley, M Davies, Pratley, Reo-Coker, Muamba, Eagles, Miyaichi, Petrov, K Davies, Klasnic, Tuncay, Ngog, Blake, Sordell.
Wigan (from): Al Habsi, Pollitt, Kirkland, Caldwell, Stam, Boyce, Figueroa, Alcaraz, Lopez, Gohouri, Jones, Beausejour, Moses, Gomez, McArthur, McCarthy, Diame, Watson, Thomas, McManaman, Di Santo, Rodallega, Sammon, Maloney, Crusat.
Fulham vs Stoke
Recent signing Pavel Pogrebnyak could make his Fulham debut in Saturday's Barclays Premier League clash with Stoke.
The Russia international joined from Stuttgart on transfer deadline day and could feature at Craven Cottage, although fellow striker Andrew Johnson will miss out as he continues to recover from a left adductor injury.
Philippe Senderos will miss the next couple of weeks after an MRI scan showed he has a grade two strain in his left adductor, while Zdenek Grygera (knee) and Steve Sidwell (hernia) are also unavailable.
Stoke will be without suspended defender Robert Huth.
Huth begins a three-match ban after the Potters' appeal to the Football Association against the red card he received in last weekend's 1-0 defeat to Sunderland was rejected.
Forward Cameron Jerome limped off in that game with a dead leg and midfielder Matthew Etherington missed it due to a virus, but manager Tony Pulis is hopeful both players will be available for the contest at Craven Cottage.
Fulham (from): Schwarzer, Stockdale, Etheridge, Hangeland, Riise, Kelly, Frei, Murphy, Etuhu, Gecov, Dempsey, Ruiz, Davies, Duff, Hughes, Baird, Dembele, Trotta, Kasami, Pogrebnyak.
Stoke (from): Sorensen, Begovic, Wilkinson, Shawcross, Wilson, Pennant, Delap, Palacios, Etherington, Crouch, Walters, Shotton, Upson, Diao, Jones, Whitehead, Whelan, Woodgate, Fuller, Jerome, Collins.
Tottenham vs Newcastle
Tottenham forward Rafael van der Vaart has been ruled out of Saturday's game against Newcastle after he failed to overcome the calf injury that kept him out of Monday's draw at Liverpool.
Aaron Lennon and Jermain Defoe (both hamstring) are back in the frame after missing the game at Anfield, but Younes Kaboul (knee) and Sandro (calf) are doubts.
Ledley King (knee) will be given a late fitness test, but William Gallas (calf) and Tom Huddlestone (ankle) are out.
Newcastle boss Alan Pardew will be without striker Leon Best and utility man Ryan Taylor.
Best could miss the rest of the season with the medial ligament injury he suffered against Aston Villa last weekend, while the ankle problem Taylor sustained in the same game is less serious, but will keep him out at White Hart Lane.
Yohan Cabaye completes his three-match ban, Cheick Tiote is still on African Nations Cup duty while defender Steven Taylor (Achilles) and midfielders Sylvain Marveaux (groin) and Sammy Ameobi (knee) continue their respective recoveries.
Tottenham (from): Friedel, Gomes, Cudicini, Assou-Ekotto, Rose, Kaboul, Khumalo, Walker, King, Dawson, Nelsen, Livermore, Sandro, Parker, Bale, Kranjcar, Lennon, Dos Santos, Modric, Defoe, Adebayor, Saha, Dawkins, Lancaster, Luongo.
Newcastle (from): Krul, Elliot, Harper, Simpson, Santon, Ferguson, Perch, Coloccini, Williamson, Kadar, Obertan, Ben Arfa, Gutierrez, Gosling, Abeid, Ba, Cisse, Shola Ameobi, Lovenkrands.
Wolves vs West Brom
West Brom head coach Roy Hodgson will await late fitness checks on striker Shane Long and midfielder Graham Dorrans before finalising his side for Sunday's Barclays Premier League derby at Wolves.
Long has been troubled by a back complaint and chest pains and has only been able to train on his own this week, while Dorrans is suffering from a hip problem.
Hodgson has to decide whether to give first starts to transfer deadline day signings, left-back Liam Ridgewell and midfielder Keith Andrews. Skipper Chris Brunt (ankle) and fellow midfielder Zoltan Gera (knee) are long-term absentees.
Wolves will check on the fitness of central midfielders Jamie O'Hara (groin) and Dave Edwards (thigh) before the game.
Manager Mick McCarthy is already without Emmanuel Frimpong, who returned to Arsenal after rupturing knee ligaments, and the suspended Karl Henry in that department of his side.
Winger Michael Kightly (back) is also sidelined while right-back Kevin Foley is battling to overcome an ankle problem.
Wolves (from): Hennessey, De Vries, Foley, Stearman, Doherty, Johnson, Bassong, Berra, Ward, Hammill, Hunt, O'Hara, Edwards, Forde, Jarvis, Doyle, Ebanks-Blake, Fletcher, Jonsson.
West Brom (from): Foster, Fulop, Reid, Jara-Reyes, Olsson, McAuley, Dawson, Tamas, Mattock, Ridgewell, Shorey, Mulumbu, Andrews, Morrison, Thorne, Scharner, Dorrans, Thomas, Tchoyi, Cox, Fortune, Odemwingie, Long.
Aston Villa vs Man City
Manchester City captain and defender Vincent Kompany (knee) should return for the Barclays Premier League leaders' trip to Aston Villa on Sunday.
Midfielder Samir Nasri is also in contention after leaving the field with a groin injury in last week's defeat of Fulham.
Striker Mario Balotelli is again missing as he completes a four-match suspension while midfielder Yaya Toure and defender Kolo Toure are still at the African Nations Cup.
Aston Villa are hopeful of having a trio of players back.
Striker Gabriel Agbonlahor (back and hamstring), winger Marc Albrighton (thigh) and central defender James Collins (calf) have all made good progress towards fitness during the past week.
Midfielder Chris Herd (ankle) remains the only long-term casualty. Striker Robbie Keane will make his final home appearance before returning to the Los Angeles Galaxy.
Aston Villa (from): Given, Guzan, Hutton, Lichaj, Collins, Cuellar, Dunne, Warnock, Baker, Bannan, Clark, Petrov, Ireland, Albrighton, Bent, Keane, Agbonlahor, Heskey, N'Zogbia, Weimann, Marshall, Johnson, Gardner, Stevens.
Man City (from): Hart, Pantilimon, Richards, Zabaleta, Lescott, Kompany, Savic, Clichy, Kolarov, Rekik, Milner, Nasri, Johnson, Barry, De Jong, Hargreaves, Pizarro, Silva, Dzeko, Aguero, Razak, Suarez.