French centre-forward Karim Benzema was visibly injured in the back of his right thigh on Thursday in the 60th minute of Real Madrid's game against Valencia.
Benzema, who missed the World Cup in Qatar in November and December with a left thigh injury, touched the back of his right leg after a strike on Thursday evening, and himself asked for the change.
He left at the hour mark without the help of the healers, but grimacing, and went directly to the locker room.
He was replaced by Rodrygo.
Victim of multiple muscle glitches since the start of the season, the Ballon d'Or 2022 has already missed 9 matches with Real this season in all competitions.
Real Madrid will face Liverpool in the Champions League Round of 16 on February 21.
That leaves Karim Benzema just under three weeks to recover from his injury.
At the start of the match, Brazilian central defender Eder Militao also came out injured on the merengue side, after contact with Samuel Lino.
He was replaced in the 36th by Dani Carvajal.