The French centre-back sustained the knock during the international break and has been sidelined since then.
While earlier reports suggested that Kounde could regain his fitness ahead of the Clasico, the Catalan giants are now doubting the possibility.
The 23-year-old’s rehabilitation has been slightly behind schedule, and he runs the risk of a relapse if he returns too quickly.
The news is a big blow for the Blaugrana, who are already missing several players through injuries.
Their defensive options are depleted, with Ronald Araujo and Andreas Christensen in the treatment room.
Kounde has been deployed in an unnatural right-back position since sealing a much-anticipated move from Sevilla in the summer.
His performances were highly impressive, and his absence has left manager Xavi scratching his head. Sergi Roberto has been filling in at right-back but he has struggled in the role.
The Blaugrana are desperate for a victory to keep their round of 16 hopes alive, as they are third in their group behind Bayern Munich and Inter.
The Catalan giants will then lock horns with Madrid in the first Clasico of the season this weekend.
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