Barca must beat Villareal on the weekend if they are to stand a chance of overhauling Real in the run in.
Real Madrid are aiming to remain in pole position for a first La Liga title in five years when they travel to relegated Granada on Saturday night.
Fresh from their 3-0 Champions League semi-final first leg victory over Atletico, the Merengues will be confident of keeping pace with Barcelona at the top of the table.
Zinedine Zidane’s outfit sit second, level on 81 points with the Catalans but with an inferior head-to-head record. However, have played a game fewer than their rivals.
They will be without the injured Dani Carvajal, who picked up a hamstring problem in midweek, in addition to Gareth Bale and Pepe for the trip to Andalusia.
Tony Adams’ side, meanwhile, have nothing but pride to play for, after they were condemned to the Segunda last week. Forward Adrian Ramos insists the players will look to put in a performance for their long-suffering fans.
"We have a commitment to Granada and we should be professional for the supporters. It's very hard after being relegated, but we need to stay professional and show determination, trying to give the fans something to cheer about in what's left of the season," Ramos said.
"We know they're one of the best clubs in the world, with a great squad and players that can make a difference. We just need to try and do our jobs."
Immediately before that game, Barcelona will host fifth-placed Villarreal at CampNou, in a match both sides need to win.
Barca, who welcome back captain Andres Iniesta from a thigh injury, required a last-minute Lionel Messi free kick to salvage a draw when the sides met earlier this season at the Estadio de la Ceramica. They know they must win if they are to stand a chance of overhauling Real in the run in.
The Yellow Submarine have won five of their last six, including an away victory over Atletico Madrid, as they make a late bid for the fourth and final Champions League berth with Sevilla stumbling.
Villarreal sit five points behind Jorge Sampaoli’s men with just three games to go. But with Sevilla hosting Europa League-chasing Real Sociedad on Friday there is a chance to cut the gap down even further.
Elsewhere on Saturday, third-bottom Sporting Gijon host Las Palmas knowing a defeat could see them relegated. Kings Cup finalist Alaves face Athletic Bilbao in a Basque derby on Sunday.