The contest is a historic occasion for the hosts, who are set to play their first game in the main draw of the Copa del Rey.
Match preview
Atletico Lugones have the privilege of playing host to top-flight opposition after they successfully negotiated their way through the preliminary round.
They were beaten by Badalona in the preliminary stage last season, but they had no such trouble against Pradejon, as they claimed a 2-1 victory thanks to goals from Lucas Fernandez and Pibe.
The hosts play their league football in the sixth tier of the Spanish football pyramid and the first level of the Asturian local league system.
They have experienced a difficult start to their campaign, mustering just six points from eight matches, which leaves them in the relegation zone.
However, they finally managed to claim their first league win of the season in Sunday's away meeting with Candas, ensuring they head into their midweek cup tie in a positive mood.
After Andoni Iraola opted to leave Vallecas in the summer, there were fears about whether his incumbent, Francisco, could pick up the baton and build upon his fine work, but those concerns have been allayed in the opening few months of the campaign.
Rayo, who have finished in 12th and 11th place in the last two seasons, are currently sat in eighth position with 17 points to their name from 11 matches.
Los Franjirrojos have proven to be a tough team to beat in recent weeks, having won two and drawn five of their last seven league matches since losing to Real Betis on September 2.
Former Man United player Bebe has been the hero for Rayo in the last two matches after scoring a 92nd-minute penalty to beat Las Palmas before netting a stoppage-time equaliser in Sunday's 2-2 home draw with Real Sociedad.
Rayo's next three league fixtures will take place against three of the current top-four teams - Real Madrid, Girona and Barcelona - but before they can focus on that tricky run, they will look to negotiate their way past sixth-tier opposition in the Copa del Rey, as they dream of replicating their run to the semi-finals in the 2021-22 season.
Atletico Lugones Copa del Rey form:
Atletico Lugones form (all competitions:
Rayo Vallecano form (all competitions):
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Team News
Atletico Lugones boss Christian Pito could be tempted to select the same lineup that started the win over Pradejon in the previous round.
Rafa de Diego will feature in goal for the hosts, and he will be bracing himself for a busy outing against top-flight opposition.
With Rayo set to face Real Madrid at the Santiago Bernabeu this weekend, Francisco is likely to rotate his squad for the midweek cup tie.
Bebe is likely to be given a starting berth after netting in Rayo's last two matches, while the likes of Andrei Ratiu, Pep Chavarria, Jorge de Frutos and Radamel Falcao likely to be given run outs
Randy Nteka was an unused substitute on Sunday following his return from injury, and the midfielder could also feature on Wednesday, as he looks to build up his match fitness.
Atletico Lugones possible starting lineup:
De Diego; Fernandez, Pedro, Martinez, Ramos; Deco, Basualdo, Perez, Jaime, Pibe; Rodriguez
Rayo Vallecano possible starting lineup:
Cardenas; Ratiu, Mumin, Hernandez, Chavarria; Ciss, Perez; De Frutos, Nteka, Bebe; Falcao