Dortmund’s participation in the cup competition was cut short following a 3-2 loss to Werder Bremen but that defeat has now been compounded by the loss of their inspirational skipper.
Reus limped off in the final minute of regulation time to be replaced by debutant Emre Can with Dortmund confirming the severity of the problem on social media on Wednesday afternoon.
"Captain Marco Reus contracted a muscle injury in the DFB-Pokal,” a tweet read.
"According to the current status, he will be able to start training again in around four weeks."
The news will hit Dortmund manager Lucien Favre very hard as their UEFA Champions League round of 16 first leg clash with French champions Paris Saint Germain comes off in two weeks.
Reus will however hope to be available for selection for the second leg in France on March 11.
The 30-year-old former Borussia Monchengladbach winger will also miss upcoming league games against Bayer Leverkusen, Eintracht Frankfurt, Werder Bremen and Freiburg.
Reus has played 26 times in all competitions for Borussia Dortmund this season, scoring 12 goals.
Dortmund are third on the Bundesliga table, three points behind leaders Bayern Munich.
Reus has won 44 caps for the German national team and has scored 13 goals.