La Liga will only have one representative in the quarter-finals of the Europa League after Sevilla and Villarreal play out their last-16 second leg in two days' time.
Holders Sevilla will be favourites to advance and continue their defence following a 3-1 victory in the opening leg last week.
Vitolo put the visitors in front with the fastest goal in Europa League history (13 seconds) before further strikes from Stephane Mbia and Kevin Gameiro either side of Luciano Vietto's goal gave Sevilla a commanding advantage.
Unai Emery's side are in fine form both in Europe and domestically of late, scoring three or more goals in six of their last eight games.
Sunday's 3-0 win over Elche moved Los Rojiblancos to within four points of slumping Atletico Madrid in the race for La Liga's top four.
Sevilla have also won six straight games at home in European competition and conceded just twice in that run.
They have faced Spanish opposition regularly in UEFA competition too, winning their last four ties against Liga opponents in Europe.
In last season's round-of-16 match against Real Betis, they recovered from a 2-0 first-leg home loss – a similar challenge to the one Villarreal must meet if they are to upset the odds.
The Yellow Submarine have to score three goals to stand any chance of going through and they are likely to find the net at least once as they have scored in all 11 Europa League matches they have been involved in this season.
However, their overall form has dipped of late with just one win in their last five games in all competitions.
Away from home in Europe this season, Villarreal have won three of their five games and all three triumphs have been by two or more goals - something they must replicate on Thursday.
Both sides have one player suspended, with Grzegorz Krychowiak missing for the hosts and Jaume Costa absent for the visitors.
This will be the third meeting between the two sides this season and Sevilla have won both so far.
Sevilla:
Form in Europa League: WLWWWW
Form in all competitions: LWDWWW
Possible starting lineup: Rico; Coke, Kolodziejczak, Pareja, Navarro; Banega, Iborra, Mbia; Vidal, Gameiro, Vitolo
Villarreal:
Form in Europa League: LDWWWL
Form in all competitions: WDLWLD
Possible starting lineup: Asenjo; Mario, Musacchio, Bailly, Rukavina; Jonathan dos Santos, Trigueros, Pina, Cheryshev; Vietto, Giovani dos Santos
Sports Mole says: 2-2