Valencia coach Ernesto Valverde has said his side must assume they will have to win away to Sevilla on Saturday if they are to secure fourth place and Champions League qualification for next season.
Los Che go into the final day of the Spanish season two points ahead of Real Sociedad, who travel to relegation-threatened Deportivo la Coruna.
With Real boasting a superior head-to-head record in their meetings with Valencia this season, the San Sebastian club will qualify for the Champions League if the two teams finish level on points.
That means a draw for Valencia will not suffice if La Real win at the Riazor.
And Valverde believes his side will have to register a fifth consecutive victory if they are to ensure they are playing amongst Europe's elite next season.
"We know that Deportivo are playing for survival, but we have to assume that in a game in which both sides are playing for a lot that Real Sociedad will win," he told a press conference on Thursday.
"We can't imagine another situation because it would be very dangerous."
Valencia will be without Andres Guardado as he has already flown out to join up with Mexico ahead of their World Cup qualifier with Jamaica on June 5, whilst Tino Costa and Nelson Valdez are both injury doubts.
Real Sociedad, meanwhile, have to hope for a favour from Sevilla and have the added complication of facing a Depor side that know they will guarantee their top-flight status with a win.
Deportivo coach Fernando Vazquez is hoping his players will feed off the atmosphere at the Riazor rather than being intimidated by the situation they find themselves in.
"The players need to think that we have an extraordinary match in a super atmosphere," he said on Thursday.
"We need to treat this as a positive target, I don't want to think about what happens if we fail.
"We have a great chance and the players and fans ought to come with this positive energy."
Should Depor fail to win, the door would be open for their Galician rivals Celta Vigo, Real Zaragoza or Mallorca to save themselves with no side yet mathematically relegated.
Moreover, all three have winnable games at home against opposition with nothing to play for as Celta and Mallorca face mid-table Espanyol and Valladolid respectively, whilst Zaragoza host third-placed Atletico Madrid.
Celta are best positioned to save themselves should Depor slip-up as they are just one point behind their Galician neighbours and tied with Zaragoza on 34 points, but have a better head-to-head record against Zaragoza.
Mallorca, meanwhile, must hope that neither Celta nor Zaragoza win and Depor lose to have any chance of survival.
Earlier on Saturday, Barcelona will look to round off their championship-winning season by matching Real Madrid's record 100 points total from last season when they host Malaga.
There is sure to be an emotional farewell to Eric Abidal at the Camp Nou as he plays his last game in a Barca shirt after announcing on Thursday that he is to leave the club at the end of the season.
Victor Valdes is also expected to take his place in goal for the final time at the Camp Nou as he looks set to move on after more than 500 appearances for the club.
And there will be more goodbyes in the Spanish capital when Jose Mourinho takes charge of Real Madrid for the final time when they host Osasuna on Saturday.
The self-proclaimed "Special One" is expected to get a frosty reception at the Santiago Bernabeu as Real return home for the first time since they lost the Copa del Rey final to Atletico Madrid and the Portuguese's departure was confirmed.
Saturday (all kick-offs 1900 GMT unless stated)
Real Madrid v Osasuna (1500 GMT), Barcelona v Malaga (1700 GMT), Celta Vigo v Espanyol, Granada v Getafe, Sevilla v Valencia, Deportivo la Coruna v Real Sociedad, Mallorca v Valladolid, Real Zaragoza v Atletico Madrid, Levante v Real Betis, Rayo Vallecano v Athletic Bilbao