The 24-year-old recovered from flu to start for the defending German champions against Schalke in the Bundesliga on Saturday.
However, the centre-back suffered a partially-torn ankle ligament just 30 minutes into the match that ended in a 2-1 defeat for Dortmund and was substituted at half time.
"It was not like he directly signalled he could not carry on," coach Jurgen Klopp told reporters. "It hurt, sometimes more and sometimes less. That's why he tried to play the clock down and have a look at it during half time."
Dortmund are currently 20 points behind leaders Bayern Munich in second place in the Bundesliga table.