Carlo Ancelotti's side have not lost in the league in 12 games, a run stretching back to October. Last weekend's draw at Athletic Bilbao means that they sit joint-second in the standings with rivals Barcelona.
Villarreal moved to within three points of the Champions League qualification places with a 3-1 success over Osasuna on Monday.
The hosts head into this match off the back of an impressive 3-0 victory over city rivals Atletico Madrid in the Copa del Rey.
Ancelotti is expected to make changes to his side, with Diego Lopez set to return in goal and Daniel Carvajal in line to start at right-back. Gareth Bale could also feature after the Welshman missed the midweek win with a calf problem.
Real Madrid: WWWWWD
Possible starting lineups
Real Madrid: Lopez; Carvajal, Pepe, Ramos, Marcelo; Modric, Alonso; Bale, Di Maria, Ronaldo; Benzema
Villarreal: Asenjo; Mario, Gabriel, Dorado, Costa; Ramos, Trigueros; Aquino, Gomez, Giovani; Perbet
Sports Mole says: 3-1