The focus of attention will fall on Barcelona, and most significantly the out-of-sorts Lionel Messi, as they look to salvage their season with a difficult trip to Athletic Bilbao on Sunday.
The Primera Division is Barcelona's last chance to claim major silverware in Gerardo Martino's first season in charge, following their last-gasp 2-1 defeat to Real Madrid in Wednesday night's Copa del Rey final.
Messi was again a peripheral figure at the Mestalla as Madrid's world-record signing Gareth Bale stole the acclaim with his stunning late goal.
Real Madrid winger Angel Di Maria spoke to his Argentina team-mate after the match and, despite suggestions he is unhappy at the Nou Camp, believes the only concern Messi has is turning Barcelona's season around in the next month.
"I talked to him [after the cup final] and he's calm and happy," Di Maria told Radio America.
"I think that things aren't going well for Barca and that affects him and it shows.
"Moreover opponents know him better than ever and that counts too. I don't think Leo is having a hard time."
With Madrid inactive this weekend - as they prepare for a Champions League semi-final against Bayern Munich - Barcelona can move above them and into second place as they try to chase down leaders Atletico Madrid over the final five games of the La Liga season.
Atletico host Elche on Friday night - in a match moved forward a day to accommodate their own Champions League exploits against Chelsea - and will open a six-point gap over their rivals with victory.
Star striker Diego Costa could return from his leg injury for the match and revealed coach Diego Simeone has called on his players to remain fully focused on lowly Elche, despite the lure of their meeting with Chelsea in midweek.
"The coach said it's a final (against Elche) so we have to treat it like one because it's a very important game," Costa told AS.
"Elche are an opponent who are always complicated and they have a good team, but we will try to play our game.
"At home, with the supporters, we are very strong."
Sevilla will be hoping Barcelona can get back to winning ways as they make their late-season push for a Champions League place.
Unai Emery's in-form side head into the weekend six points behind fourth-placed Athletic, but can halve that deficit when they host Granada immediately before kick-off at San Mames on Sunday night.
In the relegation fight, last-placed Real Betis cannot be relegated this weekend but must almost certainly win at Rayo Vallecano.
Betis are 10 points from safety but Real Valladolid's weekend off means they will have at least a week's stay of execution.
Valladolid could be the only team they could catch by the end of the weekend, though, with Osasuna at home to Valenica, who have an approaching midweek Europa League tie with Sevilla in the back of their minds.
Getafe and Almeria, both inside the bottom three, would also move ahead of Valladolid with wins this weekend.
Mid-table opposition await both teams with Getafe at Levante while Almeria are at home to Celta Vigo.
Real Sociedad can move closer to a European place when they host Espanyol, while on Monday night Malaga are at home to Villarreal.