Barcelona have confirmed that Rafinha suffered a torn anterior cruciate ligament during the 1-1 Champions League draw with Roma on Tuesday.
Rafinha was a 62nd-minute replacement for Ivan Rakitic at the Stadio Olimpico but was stretchered off shortly after following a heavy challenge from Radja Nainggolan.
Barca coach Luis Enrique admitted after the match that he was concerned the problem could be serious and the club announced early on Thursday that tests have revealed a ligament tear.
The player will undergo surgery in the coming days and, while Barca have so far set no timeframe on his recovery, early reports in Spain suggest he could be sidelined until close to the end of the season.
The news comes as a bitter blow to the Spanish and European champions given they are unable to field any new signings until January 2016 as a result of their FIFA-imposed transfer ban.
Rafinha, 22, has made six appearances in all competitions for Barca so far this season, scoring once.