Carlo Ancelotti's men thumped cross-city rivals Atletico Madrid in the Copa del Rey on Wednesday night but they must forget that and turn attention to the weekend fixture with an in-form Villarreal side.
Following last weekend's 1-1 draw with Athletic Bilbao, Ancelotti will have to go without Cristiano Ronaldo on Saturday after he was suspended for three games following an altercation with Carlos Gurpegi and that means relying heavily on the likes of Angel Di Maria, Karim Benzema and the superb Jese Rodriguez.
The draw with Athletic Bilbao left Los Blancos in third place, level on points with Barcelona but behind due to goal difference. Both teams are now three points adrift of league leaders Atletico Madrid.
A win for Madrid would put them top, that is unless Atletico Madrid can go on to beat Almeria later on Saturday evening and also depend on Barcelona's result at Sevilla.
Villarreal, have done considerably well in their return to La LIga and are fighting with the likes of Athletic Bilbao and Real Sociedad for a Champions League place, sitting fifth, just three points behind fourth place after winning four of their last five La Liga games.
The two sides met earlier in the season at El Madrigal, a resilient Villarreal held Ancelotti's men as Ronaldo and Gareth Bale, despite scoring one each found it hard to break down a defence mastered by Mateo Mussachio.
As mentioned, Ronaldo will miss this game but it is expected that Bale will be available following a string of injury problems.
The visitors, must do without talented striker Ikechukwu Uche, who has a thigh strain, while midfielder Tomas Pina will also miss out due to suspension.