Barcelona, who top the table by one point, could retain their La Liga crown with a victory away to Sevilla, if Real Madrid fail to beat Athletic Bilbao at the Bernabeu.
Coach Pep Guardiola has doubts over midfielder Xavi and defender Gerard Pique who have been nursing muscle injuries.
He also has to decide whether to stand by misfiring Swedish striker Zlatan Ibrahimovic in attack, with Bojan Krkic having been in great form recently.
Fourth-placed Sevilla, in Spain's last available Champions League qualification spot, have more at stake than Barca, their president Jose Maria del Nido told the club's website.
"Barcelona have a lot to play for, but we have much more," he said. "Barca have won many league titles whereas we have hardly ever played in Europe's top club competition, unfortunately. It would only be our fourth time."
Top scorer Luis Fabiano returned to their squad after the Brazil striker recovered from an ankle injury.
Real host a Bilbao side who are chasing a place in next season's Europa League, and are trying to isolate themselves from speculation over Barca's game at the Sanchez Pizjuan.
"Tomorrow will go a long way towards deciding the league," coach Manuel Pellegrini told reporters. "All we are focused on is beating Bilbao."
Real Mallorca are one point behind Sevilla in fifth and are the only team who can overtake them. They visit a Deportivo La Coruna side who have not won in their last 11 matches.
"Obviously it depends on what happens in the Sevilla game but we also have to win," coach Gregorio Manzano said. "We've only lost two games in the last 10, but Depor will want to finish the season (in front of their own fans) with a win."
Atletico Madrid visit Sporting Gijon with one eye on Wednesday's Europa League final against Fulham, and have left Sergio Aguero, Diego Forlan, Simao, Paulo Assuncao and Luis Perea out of their squad.
"It's more than likely some players will get debuts. It is necessary to rest others because of tiredness and knocks," coach Quique Sanchez Flores told reporters. "Sporting still have something to play for so we are taking the game seriously."
Osasuna president Patxi Izco was returned for a third term on Friday and confirmed that former Spain boss Jose Antonio Camacho would continue as coach for next season.
"He has met his objectives (they are safe from relegation), he knows the squad, and we believe that in his third year he will be able to get the most out of the team," Izco said.
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