Midfielder Konstantinos Karetsas came on for Guirassy in the 34th minute of the match. The Greek played just behind Fabio Silva, Borussia Dortmund's lone striker from then on.
In the third minute, Guirassy appeared to pick up the injury when he slid just past the ball in the five-metre box after a cross from Julian Ryerson on the right, then crashed awkwardly into the near post.
Initially, he seemed unaffected, but his discomfort worsened as the match went on. After almost half an hour, Guirassy grabbed his thigh and signalled that he was having problems.
Several minutes passed before he came off. Konstantinos Karetsas had already taken off his warm-up bib when Kovac urged patience, hoping Guirassy could carry on. But after discussions on the touchline and an attempt to play on, Guirassy came off for Karetsas with the score at 0-0.
How many goals has Serhou Guirassy scored for BVB this season?
With six points from three Champions League matches, BVB have now lost their top scorer to injury: the 30-year-old former Stuttgart player has eight goals and two assists in 14 competitive matches this season. His Champions League return stands out, with four goals in the first three matchdays.
Getty ImagesGuirassy joins a fairly long list of Dortmund players who have come off injured this season, some with serious injuries. The list includes Karetsas, his compatriot Giannis Konstantelias and defender Filippo Mane.
At short notice, BVB also had to manage without midfielder Marcel Sabitzer against Betis, with illness ruling him out. Kovac's side face promoted SV Elversberg in the Bundesliga on Saturday afternoon before the final international break of the year.