Published: 2019-08-29 04:55:59 BdST
The 27-year-old Spain international, who has featured in both of Real's games so far, joins a growing injury list at the Santiago Bernabeu just two weeks into the new campaign.
"Our player has been diagnosed with a muscular injury in the right femoral biceps. His recovery will continue to be monitored," read a club statement on Wednesday.
Isco joins James Rodriguez, who has been ruled out of the weekend trip to Villarreal with a calf injury, on the sidelines.
Attacking midfielder Marco Asensio is likely to miss the rest of the campaign with a knee injury picked up in pre-season.
New signings Eden Hazard and Rodrygo have yet to make their debuts due to muscle problems while back-up striker Mariano Diaz has a similar issue and none are likely to feature on Sunday.