Meanwhile, Getafe are set to return to the city of Seville just days after losing 1-0 to Sevilla at the Ramon Sanchez Pizjuan.
Match preview
Betis went into the international break without a league victory after they had to settle for just two points from their opening three matches.
They drew 1-1 with Girona and played out a goalless affair with Alaves, before they fell to a 2-0 away defeat against Real Madrid in their final outing before the international period.
Following the two-week break, Los Verdilblancos finally claimed their first league win in Friday's home outing against newly-promoted Leganes.
Abde Ezzalzouli broke the deadlock in the 72nd minute, before Barcelona loanee Vitor Roque netted his first Betis goal to wrap up a 2-0 home victory, moving Manuel Pellegrini's side up to 11th spot.
Betis know that another victory on Wednesday would move them up to sixth position, but claiming maximum points may be easier said than done after failing to win any of their previous three games against Getafe (D2, L1).
Getafe are languishing in the relegation zone after mustering three points from their first four matches of the 2024-25 season.
Jose Bordalas's side found it tough to offer a threat in the final third, having gone three matches without a goal since Christantus Uche scored in a 1-1 draw against Athletic Bilbao on matchday one.
The Azulones went on to play out consecutive goalless home draws against Rayo Vallecano and Real Sociedad, before suffering a narrow 1-0 defeat in Saturday's away meeting with Sevilla.
As a result of that loss, Getafe have now gone nine matches without a league win since recording a 3-1 away win over Almeria at the end of April.
They have also won just two away La Liga games since the start of last season, suggesting that it will be a difficult task to claim maximum points in their second trip to Andalusia in five days.
Real Betis La Liga form:
D
D
L
W
Real Betis form (all competitions):
D
W
D
W
L
W
Getafe La Liga form:
D
D
D
L
Team News
Earlier this month, Betis playmaker Isco underwent a second surgery on a leg injury that he sustained at the end of last season, and his return is now expected to be delayed until January.
William Carvalho is set to miss the rest of the 2024-25 campaign after tearing his right Achilles tendon in Friday's win over Leganes.
Isco and Carvalho are joined on the sidelines by defender Marc Barta, but Cedric Bakambu and Juanmi have overcome their injury issues and should feature in the matchday squad.
Roque could be given the chance to make his first Betis start after coming off the bench to find the net against Leganes.
As for Getafe, defender Omar Alderete is at risk of missing a second straight game with a knee injury that he sustained while on international duty with Paraguay.
The visitors are also likely to be without the services of Nabil Aberdin, Borja Mayoral and Real Madrid loanee Alvaro Rodriguez, with the latter waiting to make his debut after arriving at the end of the transfer window.
With his team struggling for goals, Bordalas may decide to freshen up his attack with the introduction of Peter Federico.
Real Betis possible starting lineup:
Silva; Bellerin, Llorente, Natan, Rodriguez; Cardoso, Altimira; Fornals, Lo Celso, Abde; Roque
Getafe possible starting lineup:
Soria; Iglesias, Djene, Berrocal, Rico; Uche, Arambarri, Milla; Perez, Federico, Yildirim
We say: Real Betis 2-0 Getafe
Betis will be in a positive mood after claiming their first league win of the season on Friday, and we think that they will back up that result by clinching another win against a Getafe side that will be low on confidence after failing to win any of their first four matches.