Previews: Stakes high ahead of East Coast derby
Villarreal host near neighbours Valencia on Saturday with a place in next season's Champions League the prime objective for both clubs.
The teams are tied on 59 points, two behind Atletico Madrid in fourth, with two matches left to play.
"Only a win is of use to either team," striker Joseba Llorente told reporters.
Atletico Madrid have won four in a row to take the last Champions League qualification slot and still have an outside chance of making it an automatic place by overhauling third-placed Sevilla.
They visit beaten King's Cup finalists Athletic Bilbao on Saturday, who are mathematically safe from relegation.
Sevilla, who can assure third place with a win, named strikers Frederic Kanoute and Ernesto Chevanton in their squad to host Deportivo Coruna on Saturday.
The Mali international had been struggling with a groin strain during the week. Uruguayan Chevanton has been out since February after knee surgery.
Sporting Gijon ended a run of eight matches without a win by beating Malaga 2-1 last weekend to climb out of the relegation places up to 17th. They will hope to build on that result when they travel to face Real Valladolid on Saturday.
Sporting midfielder Sergio Matabuena will be able to play after his yellow card from last weekend was overturned on appeal.
Osasuna's battle to avoid the drop faces a tough test on Saturday when they visit champions Barcelona, who will be celebrating winning the title in front of their own fans at the Nou Camp.
Osasuna, who are 18th on the same number of points as Sporting, are without suspended defender Sergio Fernandez but are expected to have Iranian forward Masoud available after injury.
Numancia, 19th, are two points from safety and three short of Getafe in 16th ahead of their trip to the Coliseum on Saturday.
Getafe coach Michel told reporters: "I am convinced if we win this game we will avoid relegation."
Bottom club Recreativo Huelva will be relegated if they fail to beat Racing Santander at home on Saturday. They are four points from safety.
Their leading scorers Adrian Colunga and Javier Camunas are both struggling with injuries.