Carlo Ancelotti's side was dumped out of the cup by city rival Atletico earlier this week, but remains top of La Liga by a point from Barcelona.
With one less competition to worry about, Real's focus immediately switches back to the league as it looks to secure a first domestic title since 2012, and a healthy record against Getafe will give it confidence of taking all three points.
Real has won 10 of the last 11 meetings between the sides, triumphing by at least a three-goal margin in the three most recent clashes.
Getafe also enters this weekend's encounter in poor form, with no league win in its last eight matches - a run that stretches back to late October.
Barcelona is in position to capitalise should Madrid drop any points this weekend, with Luis Enrique's side also on its travels as it visits Deportivo La Coruna.
After losing to Real Sociedad earlier this month, Barca beat Atletico to ensure it remains second, and a ninth game unbeaten against Deportivo would ensure Diego Simeone's men stay behind the Catalan club.
Buoyed by a triumph over Madrid, Atletico Madrid appears to have a presentable opportunity to put its league loss to Barcelona behind it when it faces beleaguered Granada.
Third-placed Atletico will hope Fernando Torres reproduces the form that saw him score twice at The Santiago Bernabeu, and the striker is likely to fancy his chances against the division's bottom side.
Atletico can ill-afford to lose further ground on Real, which is already four points clear of its rivals with a game in hand.
Joseba Aguado will take temporary charge of Granada after coach Joaquin Caparros was dismissed on Friday after a run of two wins in 18 matches.
Fellow struggler Elche and Levante go head-to-head this weekend, with three points likely to lift the winners out of the bottom three, especially as 17th-placed Almeria travels to Valencia.
Four teams keen to keep the relegation battle at arm's length meet in two mid-table battles, with David Moyes's improving Real Sociedad entertaining Rayo Vallecano, which is just a point ahead of it, and Celta Vigo travelling to Espanyol.
Sevilla will hope to strengthen its grip on a top-four place against Malaga at Estadio Ramon Sanchez Pizjuan, while Villarreal meets Athletic Bilbao.
