Marcelino's men have won four of their last five La Liga matches and head to the Spanish capital in strong form.
Diego Simeone's side, meanwhile, are second in the table and will be looking for a victory to consolidate that position and keep them above arch-rivals Real Madrid with Barcelona having almost sewn up another title,
No team has won more home games than Los Rojiblancos in the Spanish top flight this term and William Hill price the hosts at 9/10 (1.90) for what would be their 14th victory of the season in front of their own fans.
The hosts remain without the suspended Diego Costa, who will not play again this season along with defender Lucas Hernandez who has been operated on. Jose Maria Gimenez picked up an injury in the weekend win at Eibar and will also miss out.
Los Che have their first choice centre-forward suspended, with Rodrigo Moreno sidelined following two yellow cards at Real Betis on Sunday. Midfielder Geoffrey Kondogbia and winger Denis Cheryshev are also out.
Atletico's defensive record at home this season has been exceptional and their total of seven goals conceded in 16 games is the lowest in the division.
Simeone's side have won eight of their last nine home games, keeping clean sheets in all eight of those victories.
Valencia, however, arrive in the Spanish capital having scored in eight of their last nine away games in La Liga - including twice at Camp Nou in February.
Opposing Atletico to keep a clean sheet at home this season has not been a profitable exercise, but the visitors on Wednesday have some serious momentum and at the very least should be able to get on the scoresheet.
Tips and predictions
Atletico have scored in every home game this season, so we can almost take for granted they will do so once more. This bet has paid out in seven of Valencia's last nine away games, as well as in the meeting between these sides at Mestalla earlier in the season.