Barcelona, fresh from their controversial Champions League semi-final victory over Chelsea, will be crowned Spanish league champions for the 19th time on Sunday if results go their way.
Barcelona are brimming with confidence after an unforgettable five days in which they thrashed rivals Real 6-2 in their own backyard before Andres Iniesta?s sensational stoppage-time goal put 10-man Barca into the Champions League final.
"Football won over strength and we never let our heads drop," said Brazilian Dani Alves, who will miss the May 27 final against Manchester United through suspension.
"In life you can?t waste opportunities and we have to work hard now to win the treble."
Should they succeed, Barcelona would become the first Spanish team to win the treble and it would be an incredible achievement for coach Josep Guardiola in his debut season.
Villarreal will hope to bring Barcelona crashing back to earth on Sunday and need all three points as they scramble to get into the Champions League places. As it stands, Villarreal are just a point behind fourth-placed Valencia as are Atletico Madrid.
Champions Real travel to Valencia on Saturday, trying to forget last weekend?s 6-2 humiliation by Barcelona.
After that game coach Juande Ramos admitted that Real Madrid were no longer among Europe?s elite, citing the heavy defeats to Liverpool (5-0 on aggregate in the last 16 of the Champions League) and Barcelona (6-2) as evidence, and widespread changes are expected this summer.
"Madrid are the best team in the world and we have to recover the prestige of fighting with the best sides in the world," said striker Gonzalo Higuain. "If we want to achieve that we have to improve things.
"For now we have to fight until the end of the season for our fans. It is going to be difficult to come back in the title race but we have to try as we are Real Madrid."
Valencia are desperately clinging to fourth with four games left and will hope a wounded Real don?t take out their frustration at the Mestalla Stadium.
The spotlight will be on Valencia striker David Villa who has been linked with a move to Real this summer if Florentino Perez, one of the favourites to win this summer?s presidential elections, can bankroll the move.
Atletico are a point behind Valencia but host an Espanyol side that have won five and drawn once in their last six games to surge out of the relegation zone.
Espanyol sit four points clear of trouble and are one of eight teams fighting to stay in the division.
Two strugglers meet in a crucial fixture on Sunday when Getafe, fourth from bottom, entertain Osasuna who are one place above and two points better off.
"I have no doubt that we are going to win this Sunday against Osasuna," said Getafe defender Cata Diez. "I think we will win the other games too to avoid the drop."
Real Betis are just three points clear of the drop zone and on Saturday travel to face an Athletic Bilbao side that are gearing up for the Kings Cup final.
"We have the most eagerly anticipated game in Pais Vasco (the Basque country in the north of Spain) for 25 years but that is not to say we won?t go out to beat Betis," said Bilbao coach Joaquin Caparros.
"The best way to prepare for the game against Barca, who are without a doubt the best team in the world at the moment, is to boost morale by winning."
Sevilla v Real Mallorca 1800 GMT, Athletic Bilbao v Real Betis 1800 GMT, Valencia v Real Madrid 2000 GMT
Sunday (all 1500 GMT unless stated)
Getafe v Osasuna, Recreativo Huelva v Deportivo La Coruna, Valladolid v Numancia, Malaga v Racing Santander, Almeria v Sporting Gijon, Barcelona v Villarreal (1700 GMT), Atletico Madrid v Espanyol (1900 GMT)
Source: AFP Global Edition