Real can extend their lead at the top before Barca and Atletico kick off and set a La Liga record with a 17th straight win at home to Villarreal earlier on Wednesday.
Cristiano Ronaldo and Gareth Bale missed Sunday’s 2-0 win at Espanyol due to illness and injury respectively. However, both returned to training on Monday and are expected to start.
Victory at the weekend saw Real set a new club record for consecutive league wins and match the 16 straight wins Barcelona managed under Pep Guardiola in 2010-11.
Villarreal, though, are unbeaten in the league this season as back-to-back wins have taken the Yellow Submarine up to sixth after a disrupted pre-season due to the sacking of coach Marcelino days before the campaign got under way.
Sevilla can move up to second on Tuesday if they continue their dominance of the Seville derby over Real Betis.
The Europa League holders haven’t lost in the league to Betis in four years and are strong favourites for one of Spain’s most passionate encounters.
At the bottom of the table Valencia are looking to pick up their first points of the season when Alaves visit the Mestalla on Thursday with Valencia boss Pako Ayestaran’s job on the line.