Atletico Madrid can take another huge step towards their first La Liga title in 18 years when they travel to face Valencia at the Mestalla on Sunday.
Diego Simeone's men need to win just three of their remaining four games to mathematically seal the championship.
However, Simeone's task this weekend is complicated by one of his side's most difficult away trips of the season falling between the two legs of Atletico's Champions League semi-final against Chelsea.
Midfielder Jose Sosa, though, believes five days rest will be more than enough to ensure they are in the right condition to secure a ninth straight league win.
"The coaching staff are handling that aspect well with the players that have played the most minutes.
"Those that played on Tuesday will have a bit more rest in the days before the game to ensure they are ready to play at any moment," he told a press conference on Thursday.
"We need to rest and give the second leg the attention the semi-finals of the Champions League deserves, but we need to maintain the same focus in La Liga because at this stage of the season we cannot relax."
The likes of Sosa, David Villa, Arda Turan and Tiago are likely to be drafted into the side that started Tuesday's 0-0 draw at home to Chelsea, whilst captain Gabi is certain to start as he is suspended for the second leg at Stanford Bridge.
Barcelona were the one side of the three title hopefuls not in Champions League action in midweek after falling to Atletico in the quarter-finals.
The Catalans lie four points behind Atletico in second place, albeit having played a game more than third-placed Real Madrid, and defender Marc Bartra insists they must maintain the pressure on the league leaders when they travel to Villarreal on Sunday.
"We are conscious that the four games left are finals for us and the best thing we can do is play with a lot of desire in those games and be there in case Atletico Madrid slip-up so we can put the pressure on them. We still have hopes of winning the league," he said.
"We have shown that in no way will we through away the league. The win against Athletic last week showed a lot of courage and heart to remain in the fight. We are ambitious and will give everything to win it."
Barca will still be without the injured Jordi Alba, Neymar, Carles Puyol and Gerard Pique, but will be boosted by the return of Sergio Busquets from suspension.
Real Madrid are the first of the title contenders in action this weekend as when they host struggling Osasuna at the Santiago Bernabeu on Saturday evening.
Madrid boss Carlo Ancelotti is likely to make a series of changes with his side's Champions League semi-final, second leg against Bayern Munich in mind as Los Blancos take a 1-0 first leg advantage to Germany on Tuesday.
Cristiano Ronaldo is expected to be rested as Ancelotti admitted he played against Bayern in midweek despite not being full-fit.
Gareth Bale should return to the starting line-up after recovering from flu, whilst Raphael Varane, Nacho and Asier Illarramendi are also in contention to start.
Arguably the game of the weekend involves those just below the top three, however, as Athletic Bilbao host Sevilla in a virtual playoff for the fourth and final Champions League spot.
The Basque side lead Europa League semi-finalists Sevilla by three points, but a win for Unai Emery's men away at San Mames on Sunday would take them into fourth thanks to a better head-to-head record.
Fixtures (all times GMT)
Elche v Levante (1900)
Granada v Rayo Vallecano (1400)
Getafe v Malaga (1600)
Real Madrid v Osasuna (1800)
Real Betis v Real Sociedad (2000)
Espanyol v Almeria (1000)
Valencia v Atletico Madrid (1500)
Athletic Bilbao v Sevilla (1700)
Villarreal v Barcelona (1900)
Celta Vigo v Valladolid (2000)