Madrid head coach Zinedine Zidane has named his 19-man panel for the game, with Gareth Bale also ruled out due to injury.
Bale picked up a calf injury at the weekend, lasting just 35 minutes of the defeat to Barcelona, and has been sidelined for three weeks.
With both Ronaldo and Bale absent, Zidane will likely call upon Karim Benzema and Alvaro Morata to provide firepower up front.
Sergio Ramos misses out due to his red card against rivals Barcelona on Sunday. The defender was sent off as Barcelona won El Clasico 3-2 in stoppage time thanks to Lionel Messi's 500th competitive goal for the Catalan side.
Ramos is likely to return on Saturday as Real Madrid host Valencia after being handed just a one-match suspension for his challenge on Messi during El Clasico.
Barcelona currently sit at the top of the table, level on 75 points with Madrid, but Zidane's side have a game-in-hand over their title rivals. Luis Enrique's team host Osasuna on Wednesday, with the match finishing before Real's away game with Deportivo kicks off.