The 29-year-old, who was making his first appearance of the campaign after sustaining a similar injury in pre-season, was withdrawn in the first half of the Matchday 3 stalemate in the Black Forest. An MRI scan conducted on Sunday confirmed the skipper had ruptured ankle ligaments in his right foot, ruling him out of Dortmund's upcoming games.
Schmelzer's defensive colleague Marc Bartra, meanwhile, is facing a race to be fit for BVB's UEFA Champions League clash with Tottenham Hotpsur at Wembley Stadium after picking up a groin injury at the Schwarzwald-Stadion. It is unclear when the Catalan defender will return to training, but his injury is not believed to be as serious as first feared.
Dortmund's midweek trip to London marks the first of six games in the space of just 17 days.
Watch: Nuri Sahin bemoans Dortmund's draw at Freiburg