Leaders Real Madrid travel to city neighbours Getafe in La Liga on Sunday, Barcelona visit Deportivo La Coruna.
Real Madrid make the short trip to Getafe this weekend looking to get back to winning ways after exiting the Copa del Rey on Wednesday.
Carlo Ancelotti's side were dumped out of the cup by city rivals Atletico earlier this week, but remain 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 they look to secure a first domestic title since 2012, and a healthy record against Getafe will give them confidence of taking all three points.
Real have 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 enter this weekend's encounter in poor form, with no league win in their last eight matches - a run that stretches back to late October.
Barcelona are in position to capitalise should Real drop any points this weekend, with Luis Enrique's side also on their travels as they visit Deportivo La Coruna.
After losing to Real Sociedad earlier this month, Barca beat Atletico to ensure they remain second, and a ninth game unbeaten against Deportivo would ensure Diego Simeone's men stay behind the Catalan club.
Buoyed by their triumph over Real, Atletico Madrid appear to have a presentable opportunity to put their league loss to Barcelona behind them when they face 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, who are already four points clear of their rivals with a game in hand.
Joseba Aguado will take temporary charge of Granada after coach Joaquin Caparros was dismissed on Friday following a run of two wins in 18 matches.
Fellow strugglers 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 travel to Valencia.
Seven sides are separated by just three points at the foot of the table, and Cordoba have the first chance to put distance between themselves and the bottom three on Friday when they host Eibar – the visitors looking for a third successive win.
Four teams keen to keep the relegation battle at arm's length meet in two mid-table battles, with David Moyes' improving Real Sociedad entertaining Rayo Vallecano, who are just a point ahead of them, and Celta Vigo travelling to Espanyol.
Sevilla will hope to strengthen their grip on a top-four place when they face Malaga at Estadio Ramon Sanchez Pizjuan, while Villarreal meet Athletic Bilbao.