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Real Madrid defender Eder Militao injured an anterior cruciate ligament in the 2-0 win over Athletic Bilbao on Saturday.
The Brazilian, 25, is the second Real player to sustain the same injury this week, following goalkeeper Thibaut Courtois on Thursday.
Militao was forced off early in the game after hyperextending his left knee.
The club said he will "undergo surgery in the coming days".
England midfielder Jude Bellingham scored his first goal for Real against Bilbao following his summer move from Borussia Dortmund.
The injury to Militao has left manager Carlo Ancelotti with just three fit centre-backs - David Alaba, Antonio Rudiger and Nacho.
