Barcelona defender Ronald Araujo suffered an adductor injury while on international duty, his club said Saturday, while also confirming Jules Kounde's thigh issue.
Araujo was taken off inside the first minute of Uruguay's 1-0 defeat by Iran in a friendly on Friday night, while Kounde lasted just 23 minutes of France's 2-0 Nations League win over Austria on Thursday.
The central defenders will miss their countries next matches and are likely to be unavailable for Barcelona's first games when club football resumes.
With the Clasico approaching on October 16, Barcelona coach Xavi Hernandez may need to construct a new defence.
Since he was registered to play for the Catalan side, following his summer switch from Sevilla, Kounde has become a key part of Barcelona's rearguard, often utilised at right-back.
Spanish reports suggest he will be out for at least three weeks, although the club did not specify a recovery time.
The international break has been problematic for Barca, who also saw Memphis Depay suffer a hamstring injury with the Netherlands in their 2-0 win over Poland on Thursday, while Frenkie de Jong was substituted for precaution.
