Barcelona: Villarreal guaranteed themselves a Champions League qualification spot with a 5-1 romp over Levante in La Liga on Saturday.
Diego Simeone rotated his whole team with the Champions League in mind as Atletico Madrid defeated Valencia 2-0 at Mestalla.
Marcelino's Villarreal, third, moved 18 points clear of fifth-place Real Betis, who have five games left to play.
Georges Mikautadze struck twice in the Yellow Submarine's derby victory, with Alberto Moleiro, Tajon Buchanan and Nicolas Pepe also on target.
Carlos Espi netted for Levante, 19th, provisionally three points from safety and in severe danger of relegation, with Sevilla and Alaves above them still to play this weekend.
"Congratulations to each and every one of the players. Let's continue enjoying this moment," said Marcelino, poised to leave Villarreal at the end of the season according to Spanish reports.
"Let's keep competing because we want to finish third."
Villarreal are five points clear of fourth-place Atletico, who won at Valencia despite Simeone rotating all 11 players from the Champions League semi-final first leg 1-1 draw against Arsenal.
This was match number 1000 for Simeone in his coaching career, but he was thinking more about 1001, in London on Tuesday against Mikel Arteta's Premier League leaders.
Youngsters Iker Luque and Miguel Cubo struck second half goals for Atletico, with defeated Valencia, 13th, only five points clear of the relegation zone.
Atletico took the lead after 74 minutes when Obed Vargas shuffled the ball out to Luque on the edge of the area and he produced a lethal low finish in at the near post.
The visitors doubled their advantage in the 83rd minute when substitute Antoine Griezmann teed up Cubo to thump home.
The goal was initially ruled out for offside but a VAR review showed MLS-bound striker Griezmann had timed his run in behind to perfection.
Later Saturday Liga leaders Barcelona can move to the brink of retaining the Spanish title if they win at Osasuna.
