Barcelona have confirmed that captain Andres Iniesta suffered ligament damage in his right knee during the club's ill-tempered 3-2 win over Valencia on 22 October.
Iniesta was taken off on a stretcher early in the first half at the Mestalla following a heavy challenge from Enzo Perez.
The 32-year-old is expected to be out of action for six to eight weeks and is set to miss Barcelona's next seven fixtures, including the rest of club's Champions League group games.
Catalan daily Sport reported that Iniesta could be fit in time to play the first El Clasico of the season against Real Madrid at Camp Nou on 4 December.
"The first team player Andres Iniesta has injured the lateral collateral ligament in his right knee following tests on his return to Barcelona after the team's away victory at Valencia," a statement on Barcelona's official website read.
"The midfielder is expected to be out for some six to eight weeks."
Barca boss Luis Enrique is already without the services of Gerard Pique, Jordi Alba, Rafinha, Arda Turan and goalkeeper Jasper Cillessen, who are all sidelined through injury.
Lionel Messi scored a late penalty to help Barcelona come from behind to beat Valencia at the Mestalla.
The Argentine had opened the scoring in the first half before goals from Barca loanee Munir El Haddadi and Rodrigo turned the game on its head.
Luis Suarez scored an equaliser on the hour mark and then won a penalty in injury time, which Messi converted.
"The worst thing about yesterday is Andres's injury," Messi told Sport on 23 October.
"The truth is it leaves us feeling bad. I hope Iniesta comes back soon."
The 29-year-old added: "[It] was a very hard game, when they scored the second goal against us we knew we had to turn it around in very little time and give everything to do it in such a complicated stadium to play like the Mestalla.
"Valencia created plenty of danger and had a good game."