Raphael Varane, Isco, Dani Carvajal and Marcelo are all in line to start for Real Madrid against Levante on Sunday.
Carlo Ancelotti is expected to make the changes in part to account for the exertion of the midweek internationals.
Isco would replace Angel Di Maria, who played 90 minutes for Argentina against Romania, whereas Isco played on Tuesday in Spain Under-21s’ win over Germany.
Varane would replace Pepe, who missed Portugal’s win over Cameroon through illness.
Carvajal and Marcelo would be restored to the full-back positions as part of Ancelotti’s rotation policy, with Alvaro Arbeloa and Fabio Coentrao dropping out after starting the Madrid derby.
But the Coach won’t change the front three - Gareth Bale, Cristiano Ronaldo and Karim Benzema are all expecting to play.
Think you know your Spanish football? Share your knowledge, tips and comments to win cash prizes in OLBG's World Cup tipster competition - £10,000 to be won!