The Argentina star has been ruled out until 2014, with Gerardo Martino's side hoping to end their curse of dropped points following international breaksBarcelona return to Liga action against Granada looking to avoid a dip in performance that followed the last two international breaks.
The reigning champions are undefeated in the league this season, racking up 37 points from a possible 39 in their 13 fixtures.
But Gerardo Martino's side have put in below-par showings immediately after the two previous rounds of international fixtures this term. They required a 94th-minute winner from Alexis Sanchez against Sevilla in September before playing out a 0-0 stalemate at Osasuna last month.
However, that draw at the Estadio El Sadar remains the only occasion on which Barca have dropped points this season, meaning Martino’s men - who have won their last 21 home Liga games - are sure to head into the fixture against an inconsistent Granada side with confidence.
Lucas Alcaraz's side occupy eighth in the Liga standings, winning five and losing six of their 13 fixtures this campaign.
Granada come into the match buoyed by back-to-back wins, though, with a 1-0 triumph at Levante being followed by a comfortable 3-1 success over Malaga.
They travel to Camp Nou to face a Barca side plagued by injury, with Lionel Messi (hamstring) the most notable absentee.
Messi is expected to be out until the new year and joins goalkeeper Victor Valdes (calf), defenders Gerard Pique (groin), Jordi Alba and Daniel Alves (both hamstring) and midfielder Cesc Fabregas (knee) on the sidelines.
Martino is also sweating on the fitness of Xavi (hamstring) and Cristian Tello (ankle).