The hosts have three points to their name after two matches, while Leganes have begun their campaign with a win and a draw.
Match preview
Last season, Valladolid collected 72 points from 42 matches to finish in second place in the Segunda Division, securing them a La Liga return at the first time of asking.
Having experienced relegation in their last two top-flight campaign, Valladolid's main aim will be hoping to avoid the drop for the first time since finishing in 13th spot in 2019-20.
Valladolid would have been pleased to start the new campaign with a 1-0 win over last season's Segunda Division playoff winners Espanyol, but they were unable to spring a surprise in Sunday's away clash against European champions Real Madrid.
Although Valladolid produced a battling performance, second-half goals from Federico Valverde, Brahim Diaz and Endrick condemned Paulo Pezzolano's charges to a heavy 3-0 defeat at the Santiago Bernabeu.
After experiencing a tough road trip at the weekend, Valladolid face another difficult away game in Saturday's meeting with Barcelona, and with that in mind, they will be determined to claim a positive result in Wednesday's home game against Leganes, especially as they have avoided defeat in their previous six head-to-head meetings.
Meanwhile, Leganes were promoted to the top flight as champions after they finished two points better off than Wednesday's opponents.
Los pepineros have made a promising start to their first La Liga season since 2019-20, playing out a 1-1 draw against Osasuna before edging out Las Palmas at the weekend.
Juan Cruz broke the deadlock in the 71st minute of Leganes' first home game of the season, before Enric Franquesa doubled his side's advantage to ensure a late Sandro Ramirez effort counted for very little.
Including their previous La Liga campaign, Leganes are now unbeaten in seven matches in the top flight, and they will be determined to continue that run in Wednesday's contest.
They will also be looking to claim a victory over Valladolid for the first time since recording a 1-0 home victory in April 2019.
Real Valladolid La Liga form:
W
L
Leganes La Liga form:
D
W
Team News
The hosts have reported no fresh injury concerns but are still having to cope without the services of midfielder Anuar.
Selim Amallah, Amath Ndiaye and Mamadou Sylla could return to the side after dropping down to the bench at the weekend.
Raul Moro could also be recalled to the starting lineup, and the forward will have the opportunity to score in back-to-back home La Liga matches.
As for the visitors, they bolstered their squad with the additions of Jackson Porozo, Adria Altimira and Munir last week.
Altimira made his debut at the weekend as a substitute, and he is likely to remain on the bench alongside Munir, but Borja Jimenez could be tempted to bring Porozo into his backline for Wednesday's contest.
Cruz and Franquesa are pushing for starting berths after the pair came off the bench to find the net against Las Palmas at the weekend
Real Valladolid possible starting lineup:
Hein; Perez, Comert, Boyomo, Rosa; Perez, Juric, Amallah; Ndiaye, Moro, Sylla
Leganes possible starting lineup:
Soriano; Rosier, Porozo, Gonzalez, Hernandez; Brasanac, Neyou, Cisse; Cruz, Franquesa, De la Fuente