The Poland international picked up a knock in a challenge with David Carmo in the 27th minute of the match, but he did carry on for seven minutes before the decision was made to replace him.
Lewandowski ultimately left the field in the 34th minute, with Ferran Torres entering as his replacement.
Barcelona went on to score in the latter stages of the first period, with Torres keeping his composure to find the back of the net after smart work from Ilkay Gundogan.
The Catalan outfit will be sweating when it comes to Lewandowski's fitness, though, with the experienced striker now potentially facing a period on the sidelines.
The 35-year-old was later pictured with an ice pack around his damaged ankle.
Barcelona will hope that the striker has suffered an impact injury, which would mean that he could potentially be available for the team's next match against Granada on Sunday night.
However, it now seems likely that the forward will be on the sidelines until after the international break, with Xavi's side back in action against Athletic Bilbao on October 22.
The Catalan side will then take on Shakhtar Donetsk in their third game in the group stage of the Champions League before welcoming Real Madrid in La Liga at the end of the month.
Lewandowski has again been in strong form for Barcelona this season, scoring six times and registering four assists in all competitions.
Xavi's side are already missing Pedri, Frenkie de Jong and Raphinha due to injury problems.