The 25-year-old, who started 29 league games for the German side last season, is set to be out for the majority of October after tearing muscle fibres in his left thigh on Friday.
The 2012-13 UEFA Champions League runners-up will now be without Schmelzer for their midweek clash against Marseille, as well as tough league games against Borussia Monchengladbach and Hannover 96.
However, they seemed to barely miss the defender when they faced Freiburg in the league on Saturday, with the contest ending 5-0.
The encounter saw both Marco Reus and Robert Lewandowski net braces, with Jakub Blaszczykowski following up their efforts in the 79th minute.
Dortmund will hope for a similar result against Marseille on Tuesday, with their tough Champions League group also containing both Napoli and Arsenal.
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