The 25-year-old has sustained more significant damage to his ankle than first feared and is set to be out of action until at least September.
The Germany international was ruled out of the World Cup after tearing ankle ligaments during the friendly clash with Armenia on Friday.
While it was initially hoped the 25-year-old would return to fitness during Dortmund's preseason, further tests have confirmed he has also suffered damage to his heel and that he will be out of action for three months.
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"Marco Reus will be out longer than expected. The 25-year old will have to take a break until September," read a statement on the club's official website. "[BVB team doctor] Dr. Markus Braun expects a downtime of three months."
Reus made 44 appearances in all competitions for Dortmund last season, scoring 23 goals.
He won the German players' player of the year award for his performances in the Bundesliga as Jurgen Klopp's side finished second behind champion Bayern Munich.