United were left seething after Nani's controversial red card contributed to their defeat by Real Madrid on Wednesday in the last 16 of the Champions League.
Victory over reigning champions Chelsea would certainly be a good way to end a difficult week, and one man hoping to be given the chance to prove himself will be striker Wayne Rooney.
The England forward was surprisingly left out of the starting line-up against Madrid, leading to speculation he will be shown the door by Sir Alex Ferguson in the summer.
Former United striker Michael Owen told talkSPORT radio: "If Wayne Rooney moves, where does he go to? Real Madrid, Barcelona, Bayern Munich, Manchester City, Chelsea and PSG - there's only half a dozen teams.
"It's just speculation, though. He's been dropped for one game and I'm sure he will bounce back. Obviously Wayne has got to get his head down now and start recapturing his best form.
"He's certainly got the right attitude and ability to get back into the manager's thoughts."
English Premier League champions Manchester City will be strong favourites to beat Championship strugglers Barnsley at the Etihad Stadium while, also on Saturday, Everton meet Wigan at Goodison Park.
For the Latics, it is a weekend off from the Premier League relegation battle, and one that could earn them a spot in the semi-finals for the first time in their history.
Not that manager Roberto Martinez is allowing himself to dream yet, the Spaniard saying: "Ninety minutes is an eternity in football, never mind looking to the final.
"We are happy to look back at this year's competition and how well we have done. Now, going to Goodison Park in the quarter-finals is a real challenge, and that is the way we are looking at it.
"Then, if you can overcome that, it will be the moment to look at what is ahead and what that would mean. When you are facing a game that could make history, though, for any club that is always extra special."
The other tie pits two Championship sides against each other, with Millwall hosting Blackburn on Sunday.
Saturday's FA Cup Fixtures
Everton vs Wigan
Man City vs Barnsley
Sunday's FA Cup Fixtures
Millwall vs Blackburn
Man United vs Chelsea