Zinedine Zidane faces a headache ahead of Real Madrid's trip to Villarreal on Sunday after learning that Isco could be out of action for around three weeks due to injury.
Isco's injury comes just two days after James Rodriguez also suffered a muscle problem, with Madrid already without Eden Hazard, Marco Asensio and Brahim Diaz due to various knocks.
"After the tests carried out today by the Real Madrid Medical Services, our player Isco has been diagnosed with a muscular injury in the right femoral biceps," a club statement said.
The statement added that "his recovery will continue to be monitored" but several sources told ESPN FC that the Spain international could be sidelined for around three weeks.
Club sources told ESPN FC of "some concern" about the injuries, although they believe they are not directly related to the arrival of new physical trainer, Gregory Dupont, who joined this summer from the France national team to replace Antonio Pintus, who joined Inter Milan.
Isco will miss the match against Villarreal on Sunday and will not be available for Spain national team manager Robert Moreno ahead of the internationals against Romania and Faroe Islands on Sept. 5 and 8.
In the best case, Isco would be ready to return in time to play against Levante on Sept. 14, but club sources prefer to be cautious due to his past history with muscle injuries.