Zlatan Ibrahimovic's awaited return to Barcelona was thwarted after the AC Milan striker was injured in training ahead of the clubs' Champions League game on Tuesday.
Ibrahimovic joined Barcelona before the start of the 2009-10 season in a 60 million euro transfer that also saw popular Barcelona striker Samuel Eto'o join Inter Milan as part of the deal.
But Ibrahimovic left for Milan after his only season with the Spanish champions after a falling out with coach Pep Guardiola.
Barcelona will be looking to put a domestic slip-up behind them when the defending champion faces Milan.
Real Sociedad rallied from a two-goal deficit to draw 2-2 with the Spanish champions on Saturday following weeks of speculation that Barcelona would face few challengers aside from Real Madrid as it vies for a fourth straight league title.
Barcelona defender Carles Puyol should return for the first time since May after recovering from knee surgery, but defender Gerard Pique is out injured, leaving Eric Abidal to likely fill the other center back spot.
Barcelona and Milan are favored to advance out of a group that also includes BATE Borisov of Belarus and Czech club Viktoria Plzen, who meet Tuesday in Prague.
Barcelona midfielder Thiago Alcantara said his club's intensity dropped in the second half of Saturday's draw, showing that the team many are comparing with the all-time greats is not invincible.
''If I didn't think a squad was beatable I wouldn't play football - because any team can be beaten,'' Milan midfielder Kevin-Prince Boateng told Gazzetta dello Sport. ''We've got to stay solid, because we're playing in their stadium, and play as a team, which is what we're best at.''
Alexandre Pato, Robinho and Antonio Cassano add further attacking options to the Italian champion's attack.
Former Barcelona players Mark van Bommel and Gianluca Zambrotta also return to play their former club, with Van Bommel lining up against Xavi Hernandez and Iniesta for the first time since Spain's 1-0 World Cup final victory over the Netherlands last year.
While that final in Johannesburg was remembered for the Dutch team's bruising display, Milan knows Barcelona's midfield must be held in check with Cesc Fabregas and Sergio Busquets also to worry about.
''The key players are Xavi and Iniesta - their right brain and their left brain. If you stop them it becomes difficult for their forwards to score,'' Boateng said. ''Teams can't play without their brains.''
Barcelona's attack will be without Alexis Sanchez after the Chile forward injured his thigh against Sociedad.
Boateng appears set to play despite bruising his shoulder during Milan's 2-2 draw with Lazio on Friday in its Serie A opener. Midfielder Gennaro Gattuso is questionable with an eye injury and Clarence Seedorf should also be available after sitting out against Lazio.