After defeating city rivals Atletico last weekend, Real have moved six points clear with five matches remaining, leaving them requiring just three more victories to guarantee a runners-up spot.
Valladolid face a fight to make it into the top half of the La Liga table after securing just one win in their last five games.
However, they are undefeated in their last three matches, and that could see Miroslav Dukic name an unchanged lineup for his club's trip to the Bernabeu.
Real Madrid: WWLWW
Real Valladolid: LLWDD
Possible starting lineups
Real Madrid: Diego Lopez; Sergio Ramos, Coentrao, Varane, Essien; Alonso, Modric, Ozil, Di Maria; Benzema, Higuain
Real Valladolid: Jaime, Rukavina, Marc Valiente, Balenziaga, Ebert; Rueda, Alvaro Rubio, Gonzalez, Perez, Larsson; Javi Guerra
Sports Mole says: 4-1