Atleti lead Barcelona, whom they visit on the final day, by three points at the summit, with Real Madrid a further point back in third.
The trio, who all failed to win in the same round of fixtures for the first time this season last weekend, kick off simultaneously on Sunday: Atleti at home to Malaga, Barca away to relegation-threatened Elche, and Real at mid-table Celta Vigo.
And Diego Simeone, whose side could lay their hands on the trophy should Barca fail to pick up three points, believes the whole country wants to see David outlast two Goliaths and lift the trophy at the end of the season.
"It’s not easy to break the stranglehold of two such powerful teams," said the Atleti boss. "Fans of teams all across Spain are behind us."
Malaga do not have the best of records at Vicente Calderon in the league, though two victories in the past four campaigns could give the hosts cause for concern.
Elche are unbeaten in front of their own supporters in 2014, but their last win over Barca came way back in 1974.
Lionel Messi will certainly be up for the fixture, however, as he lurks three goals behind Cristiano Ronaldo on the Liga scoring charts.
With little chance of winning the title, Real coach Carlo Ancelotti may choose to rest key players with one eye on the UEFA Champions League final.
Victory for Atleti would rule their city rivals out of the chase for the league crown.
Athletic Bilbao and Real Sociedad have secured UEFA Champions League and UEFA Europa League football respectively, so their Basque Derby will be all about bragging rights.
Antoine Griezmann and Carlos Vela, who has scored in his past three appearances, have dazzled for Sociedad this season, but in Aymeric Laporte, Bilbao have one of the most coveted young defenders in Europe.
Sociedad have won their last three derbies by two-goal margins, but Bilbao enter the latest pursuing a fifth win in six matches.
The relegation battle will recommence with Granada and Almeria, both hovering narrowly above the bottom three, doing battle, and third-bottom Getafe at home to fifth-placed Sevilla.
Real Valladolid and Osasuna know they must seize their opportunities to boost their survival hopes - they are away to relegated Betis and a desperately out-of-sorts Espanyol respectively.
The round begins with two matches of little importance on Saturday, with seventh-placed Villarreal hosting Rayo Vallecano and Valencia away at Levante.
