While the league leaders knew they would be without star forward Lionel Messi for the next few weeks before the international break, several other first-team players are either out or doubtful for Saturday.
Goalkeeper Victor Valdes and full-back Dani Alves will definitely be absent due to respective calf injuries, centre-half Gerard Pique is still struggling with a groin problem, while there are concerns over midfield duo Xavi (leg) and Cesc Fabregas (knee).
While Pique and Fabregas are expected to feature at the Nou Camp after training with the first team on Thursday, neither man has been cleared by the club's doctor.
"Unfortunately, we've had some injuries but that's why you have a big squad," defender Javier Mascherano told the club's official website.
"Everyone in the first team is ready to play. You notice the absences but that's what we're here for."
Jose Manuel Pinto is expected to make his first start of the season and fill the gap created by Valdes' absence.
Although the 38-year-old has played just 63 games in five years, Mascherano is in little doubt the former Celta Vigo custodian will prove himself a more than capable understudy to Valdes.
"We need to support Pinto, who always responds," added the Argentinian. "He's got a lot of experience and works all year to get his chance. Now he's got it.
"I've played a lot with Pinto. In my opinion, he's improved a lot in the last few years with the ball at his feet and he's had some magnificent performances."
Atletico Madrid will be looking to take advantage of any slip-up from Barcelona when they welcome Getafe to the Vicente Calderon on Saturday.
Diego Simeone's men lie three points behind the defending champions and can extend their unbeaten run in all competitions to six matches.
In order to do that, midfielder Mario Suarez has warned Atletico they cannot afford to take Getafe lightly.
"Getafe will be complicated and it's another final for us, our mentality is to go game by game," he said.
"We will continue with the same philosophy, which is the one that counts and that is helping us to be where we are."
Atletico's city rivals Real find themselves in the unfamiliar position of trailing Los Rojiblancos in the standings.
However, all eyes will be on man-of-the-moment Cristiano Ronaldo as he looks to continue his imperious form for both club and country at Almeria.
The Real forward has notched 16 goals in his 13 La Liga matches and inspired Portugal to the World Cup finals with an all-important hat-trick in their play-off against Sweden.
The Portuguese is taking nothing for granted, though, saying: "My only goal now, and that of all my team-mates, is to train so that all the Real Madrid fans continue to feel proud of their team."
Elsewhere on Saturday, Real Sociedad will be looking to move up to sixth in the standings - and above Getafe - when they take on struggling Celta Vigo, who could already be a place lower in 16th before kick-off if there is a winner in the game between Real Valladolid and Osasuna on Friday night.
The pick of Sunday's games sees Real Betis make the short trip to the Ramon Sanchez Pizjuan still smarting from a humbling 5-1 defeat to rivals Sevilla last season.
Betis will be desperate to avoid the same fate in El derbi Sevillano that they suffered 12 months ago.
Meanwhile, Valencia can extend their unbeaten run to four matches at Elche - who will be looking for their first win in five - fourth-placed Villarreal will look to stay clear of the chasing pack at Levante, and Rayo Vallecano host Espanyol.
On Monday, Athletic Bilbao travel to Malaga, who could find themselves in the relegation zone by the time they play if results go against them.