Los Che are one point behind Getafe in the final Europa League spot, while opponents Sevilla are already assured of Champions League football next season.
A disappointing campaign for Valencia could yet have a positive ending, but for that to happen they need to beat Sevilla at the very least.
Getafe, who travel to mid-table Levante on Sunday, are a point better off than Los Che and boast a superior head-to-head record.
Valencia can also catch sixth-placed Real Sociedad, who have a tougher fixture away at Atletico Madrid, so it is very much still all to play for heading into matchday 38.
Two wins in their last three, most recently holding off already-relegated Espanyol 1-0 through Kevin Gameiro's goal, means that their campaign will go down to the wire.
Sevilla face a stress-free weekend, meanwhile, as they are 10 points clear of fifth-placed Villarreal and will therefore be playing Champions League football again next term.
There is no added reward for finishing third, but Los Nervionenses will no doubt be looking to overtake Atletico - two points better off - to seal their highest league finish since 2009.
Julen Lopetegui's side were held to a goalless draw away at Real Sociedad on Thursday, bringing an end to a four-match winning run in La Liga.
The stalemate extended their unbeaten run to 16 matches in all competitions, and that momentum could come into good use as they have Europa League last-16 tie with Roma to come next month.
Sevilla do not have the best of home records against Valencia, though, going six games without a win and failing to score in four of those matches.
Sevilla's La Liga form: DWWWWWD
Valencia's La Liga form: LLDWLW
Ever Banega picked up another booking against Sociedad and will serve an automatic suspension for this final-day clash.
Winger Lucas Ocampos, who was named among the subs last time out, has been involved in five of Sevilla's last six home league goals.
The visitors are also definitely without long-term absentee Rodrigo Moreno, but Gameiro has scored one and assisted another in his last three games and will lead the line on Sunday.
Sevilla possible starting lineup:
Bounou; Navas, Kounde, Carlos, Reguilon; Gudelj, Jordan; Suso, Vazquez, Ocampos; De Jong
Valencia possible starting lineup:
Cillessen; Correia, Paulista, Guillamon, Florenzi; Kondogbia, Soler; Torres, Lee, Guedes; Gameiro
We say: Sevilla 3-2 Valencia
Sevilla are unbeaten in their last 10 home league matches, while Valencia are winless in 10 on their travels. The two previous final-day clashes between the sides were high-scoring affairs and we can see this one going the same way.