The visitors, meanwhile, will be looking to return to winning ways in the midweek La Liga clash after failing to win any of their last three competitive outings.
Match preview
Since losing to Real Madrid in the Spanish Super Cup semi-final, Atletico Madrid have embarked on a positive result of results, beginning with a 4-2 extra-time victory over Los Blancos in the last 16 of the Copa del Rey.
Atleti went on to squeeze past Granada in La Liga, before they claimed a 1-0 victory over Sevilla to progress to the Copa del Rey semi-finals.
Diego Simeone's side enjoyed another successful outing in Sunday's home clash with Valencia, as goals from Samuel Lino and Memphis Depay proved enough to secure a 2-0 victory, leaving Atleti in third position and two points clear of fifth-placed Athletic Club.
They will have the chance to extend that gap on Wednesday, before they make the short trip to the Santiago Bernabeu on Sunday for their third meeting with Real Madrid in the space of a month.
Atletico will be confident of claiming all three points in their midweek outing, having won 20 of their last 22 home league games (D2) since losing 1-0 to Barcelona in January 2022.
They have also recorded victories in 12 of their previous 15 games against Rayo, including a dominant 7-0 victory in the most recent victory between the two sides in August.
Rayo will head into Wednesday's fixture against their Madrid neighbours without a win in three matches since they claimed an extra-time victory over Huesca in the third round of the Copa del Rey.
Los Franjirrojos were subsequently dumped out of the cup by Girona, before they fell to a 2-0 home defeat to Las Palmas in La Liga.
Although they were unable to return to winning ways at the weekend, Rayo would have been pleased to see his side take a point from a tricky away fixture against a top-six side in Real Sociedad.
However, as a result of Saturday's goalless draw, Francisco's side have now failed to score in 10 of their 21 league matches, while they are also the second-lowest scorers in La Liga with just 18 goals to their name.
Despite their struggles in the final third, 12th-placed Rayo have established a sizeable eight-point gap to the bottom three, which leaves them well set to extend their stay in the top flight into a fourth consecutive season.
Rayo will be fully aware of the tough challenge that awaits on Wednesday, as they look to claim their first head-to-head win since February 2013, and their first away league victory over Atleti since recording a 2-0 victory in August 1999.
Atletico Madrid La Liga form:
L
D
W
L
W
W
Atletico Madrid form (all competitions):
W
L
W
W
W
W
Rayo Vallecano La Liga form:
D
L
L
W
L
D
Rayo Vallecano form (all competitions):
L
W
W
L
L
D
Team News
The hosts are still unable to call upon defender Cesar Azpilicueta and midfielder Thomas Lemar, who are currently sidelined with knee and Achilles injuries respectively.
Centre-back Jose Maria Gimenez is set to be out of action for two to three weeks after being forced off in Sunday's win over Valencia with a muscle injury.
Alvaro Morata is a minor doubt after he picked up a knock at the weekend, and the forward may not be risked against Rayo, with Atletico keeping one eye on Sunday's derby clash with Real Madrid.
Simeone is likely to make a number of changes due to the busy schedule, with the likes of Mario Hermoso, Alex Witsel, Marcos Llorente and Rodrigo Riquelme all in contention to start in Wednesday's contest.
As for the visitors, they are unable to call upon the injured Diego Mendez, while Pathe Ciss and Bebe are currently on international duty.
Midfielder Kike Perez is expected to replace Unai Lopez, who is set to serve a one-match suspension after receiving his fifth yellow card of the season at the weekend.
Alvaro Garcia will come back into the squad following a one-match ban, and the 31-year-old is likely to start on the left flank against Atletico.
Atletico Madrid possible starting lineup:
Oblak; Savic, Witsel, Hermoso; Llorente, De Paul, Koke, Niguez, Riquelme; Griezmann, Depay
Rayo Vallecano possible starting lineup:
Dimitrievski; Balliu, Lejeune, Hernandez, Espino; Valentin, Perez; Palazon, Trejo, Garcia; Camello