Cristiano Ronaldo and Gareth Bale will miss Real Madrid's trip to Espanyol on Sunday, coach Zinedine Zidane confirmed.
Ronaldo has a sore throat and will not travel to Catalonia as a result, while Bale is suffering from a hip problem and is being held back with Wednesday's game against Villarreal in mind.
Zidane said: "Cristiano will not travel with us, he has a sore throat, and he will stay at home. He is not ready."
Bale was substituted midway through the second half of Wednesday's last-gasp 2-1 Champions League comeback win over Sporting CP and Zidane is not willing to take any chances with the Wales international.
"He took a big blow to his hip the other day," said Zidane. "With so many games to play, we cannot take risks.
"I want to have Gareth at 100 per cent for a very difficult game on Wednesday. He might have got a bang in the same spot and be out for 10 days, or more."
Ronaldo only returned from a knee injury sustained in the Euro 2016 final for last weekend's win against Osasuna and his unavailablity is a blow for Zidane, who hinted he would be employing a rotation system this season.
The Frenchman added: "If Cristiano, Gareth and Karim [Benzema] are at 100 per cent, then they play. But that does not mean they must always play. We have many games.
"My idea is to always rotate, so that players think at any moment they will be called to play. They all need to play, that's my idea."
Bale and Ronaldo's absence may mean James Rodriguez, who came off the bench to assist Alvaro Morata's 94th-minute winner against Sporting, gets a chance to impress.
"James is training very well, he will play games," said Zidane. "Things have not changed. He is committed and wants to play."