The Bosnian was injured in Hoffenheim's 2-0 defeat to Hamburg on Wednesday, and coach Ralf Rangnick fears the worse for his top marksman.
"After the initial examinations, which are only preliminary, it seems that the anterior right ligament is partially torn,'' Hoffenheim coach Rangnick said after the game in Spain.
Ibisevic returned to Germany for further scans which will determine the extent of his injury.
If a cruciate ligament damage is confirmed, the 24-year-old striker will be probably be ruled out for the rest of the season.
So far this term, Ibisevic netted 18 goals for the newly-promoted Hoffenheim, who are widely regarded as the shock of the season in Europe.
Against all odds, Rangnick's team sensationally finished 2008 on top of the Bundesliga table, thanks to a better goal-difference than holders Bayern Munich.