Real Madrid captain Sergio Ramos has sustained a calf injury, the club said in a statement on Thursday.
Ramos was an 86th minute substitute in Spain's 3-1 win over Kosovo in a World Cup qualifier on Wednesday.
The problem puts his participation in Tuesday's Champions League quarter-final first leg at home to Liverpool and the Clasico with visitors Barcelona on April 10 in serious doubt.
"After undergoing tests, our captain Sergio Ramos has been diagnosed with an inner calf injury in his left leg," a club statement read.
The 35-year-old Ramos, who is out of contract at the end of the season, had knee surgery on a torn meniscus in January, missing 10 games, and made his comeback in last month's 3-1 Champions League last 16 second-leg victory over Atalanta.
The club did not say how long this new problem will keep him out for but media reports suggest it will be up to a month.
