The Brazillian picked up the injury in the Catalan giants' Copa del Rey round of 32 victory on Wednesday after scoring his side's third.
Barcelona winger Malcom left the pitch in tears after suffering a sprained ankle in his side’s 4-1 Copa del Rey over Cultural Leonesa.
The 21-year-old had scored for the Catalan giants to open up a three goal lead and put the tie beyond any doubt, but was unable to complete the full 90 minutes.
It is understood that he will undergo medical tests tomorrow to establish the extent of his injury.
The Brazilian has struggled to establish himself in Ernesto Valverde’s plans since moving to Spain from Bordeaux in a reported €40million (£36.5m/$48m) deal, having made just nine appearances in all competitions.
Speaking of his decision to withdraw the wide man, Valverde said: "I think it is not a hard injury. I don't know what exactly he has so I prefer to be prudent”.
Malcom’s potential absence adds to Barcelona’s injury woes, with the La Liga leaders already missing Sergi Roberto, Luis Suarez, Rafinha, Samuel Umtiti, Arthur, and Arturo Vidal.
While Roberto and Suarez are expected to be back in action before the New Year, Rafinha does not look likely to return before the end of the season. It is unclear as to when Umtiti, Arthur, and Vidal will return.
A weakened Barcelona side were rarely troubled by their visitors on a night that saw them progress to the final 16 of the Copa del Rey with little exertion.
Munir El Haddadi struck early to extend Barca’s 1-0 aggregate lead, before Denis Suarez doubled their advantage on the night. Malcom then made it three.
An unexpected consolation for Cultural Leonesa did little to turn the tide, with the Catalan giants well out of sight before Suarez added his second.
Barcelona’s next match will be a derby day clash with Espanyol on Saturday evening, with the defending champions looking to open up a gap over second-placed Sevilla, who currently lie just one point behind them.