While Real Madrid and Barcelona have firmly established a duopoly at the top of the league in recent years, Valencia and Sevilla had consistently been among the chasing pack vying for European football, but both clubs have fallen on tough times.
Valencia are in serious danger of going down for the first time since they were promoted to the Spanish top flight in 1987. They currently sit 18th in the standings with 27 points from 28 games and have won just two of their last 14 matches
They'll be looking to improve that form against Sevilla, a club they have not beaten since 2019.
"Next week we have another final," Valencia captain Jose Gaya (27) said after last week's loss to Almeria.
"After today's defeat, which hurts a lot, we have to regroup quickly to get out of the bottom, make the most of the week to prepare the game and beat Sevilla at home."
Sevilla, in Europa League action against Manchester United later on Thursday, are just five points above Valencia in 13th, though they have not lost since firing coach Jorge Sampaoli last month and appointing Jose Luis Mendilibar as his replacement.
However, they will be without mainstays Pape Gueye (24) and Marcos Acuna (31), both of whom were sent off in a 2-2 draw with Celta Vigo.
Runaway leaders Barcelona will travel to 15th-placed Getafe on Sunday as they look to get back to winning ways after spurning an opportunity to extend their lead at the top to 15 points.
After second-placed Real Madrid fell to a 3-2 defeat against Villarreal last week, Xavi's side were held to a goalless draw by mid-table Girona at Camp Nou.
Los Blancos, buoyed by a clinical 2-0 Champions League victory over Chelsea, travel to 14th-placed Cadiz on Saturday knowing full well that defeat would likely hammer the final nail into their fading title aspirations.
The defending champions will also be anxiously looking over their shoulders at city rivals Atletico Madrid, who have closed the gap between second and third to just two points following a superb 12-match unbeaten league run.
On Sunday, Atletico host 16th-placed Almeria, with Diego Simeone's red-hot side hoping to claim a sixth straight league win.