Zinedine Zidane's side thrashed Celta Vigo 6-0 at the Santiago Bernabeu last weekend, even though Cristiano Ronaldo was missing through injury.
With Barcelona beaten at Levante, Real are now 15 points behind their fierce rivals in third and three adrift of second-placed Atletico with just one round left. And in order to finish as runners-up, Madrid must beat Villarreal and hope Atletico (equal on head-to-head, but with an inferior goal difference) lose at home to Eibar on Sunday.
The main focus for Los Blancos, however, will be the Champions League final against Liverpool later this month. But here, Goal takes a look at everything you need to know ahead of Saturday's game at the Estadio de la Ceramica...
Real Madrid injuries
Ronaldo returned to training on Friday after suffering a sprained ankle against Barcelona earlier this month, which saw the Portuguese withdrawn at half-time in the Clasico. Dani Carvajal is also available again, so Zidane has a full-strength squad for the trip to Villarreal.
Real Madrid suspensions
Real Madrid do not have any players suspended for Saturday's game at the Estadio de la Ceramica.
Real Madrid potential starting line-up
Ronaldo is back from an ankle problem and "120% fit" according to Zidane, but the French coach is unlikely to start the Portuguese on Saturday.
Instead, Gareth Bale and Borja Mayoral are set to lead a second-string Madrid side in the last fixture before the Champions League final on May 26.
That should mean starts for the likes of Theo Hernandez, Achraf Hakimi, Kiko Casilla, Marcos Llorente and Mateo Kovacic, with Luka Modric, Toni Kroos, Sergio Ramos, Marcelo, Keylor Navas and more rested ahead of the big game against Liverpool next Saturday.
Villarreal team news
Villarreal are in fifth place and are guaranteed a Europa League spot, but the Yellow Submarine are keen to beat Real Madrid and finish above Betis, who are in sixth but with the same amount of points (60).
Javier Calleja's side beat Valencia 1-0 in their last home game, before a 5-1 loss at Barcelona and then a 4-2 win away to Deportivo La Coruna last weekend.
Midfielders Bruno Soriano and Ramiro Guerra are sidelined and will play no part for Villarreal on Saturday.
TV channel & kick-off time
Villarreal versus Real Madrid kicks off at 8:45pm local time on Saturday and will be shown live in the United Kingdom (UK) on Sky Sports Football from 7:40pm BST.
In the United States (US), the match is live on beIN Sports and kicks off at 2:45pm ET.
Best Opta match facts
Real Madrid have only won two of their last six league meetings versus Villarreal (drawn two, lost two), but one of those wins came at the Estadio de la Ceramica last time out in a 3-2 win in February 2017. In the corresponding fixture this season, The Yellow Submarine won 1-0 at the Santiago Bernabeu in January.
Villarreal have won their last three home league games in a row, scoring an average of 2.3 goals per game - if they win this match it would be their best run since November 2016 (five straight victories).
Since winning promotion back to La Liga in 2013-4, Villarreal have qualified for European competition in each of the last five seasons.
Gareth Bale, who made his Real Madrid debut away to Villarreal, has scored in three consecutive league appearances for the first time since April 2016 and if he nets in this game it would equal his best streak, which was set back in March 2016 (four).
No La Liga player has provided more assists than Pablo Fornals this season (12, level with Barca's Leo Messi).