De Bruyne - who is one game away from making his 250th Premier League appearance for Man City - returned to the Citizens' XI for the 0-0 draw with Arsenal on Easter Sunday after recovering from a groin injury, while Haaland has started each of the last eight top-flight matches.
However, Pep Guardiola has decided to omit the attacking pair from his starting lineup against Villa and has made a total of four changes, with Mateo Kovacic and the injured Nathan Ake also making way.
In the absence of injured goalkeeper Ederson, Stefan Ortega continues between the sticks, while Rico Lewis is handed a start at right-back, joining Manuel Akanji, Ruben Dias and Josko Gvardiol in a four-man defence.
Bernardo Silva is set to move into a central position to partner Rodri in midfield, as both Jeremy Doku and ex-Villa man Jack Grealish have been recalled to start on the flanks.
Phil Foden is therefore expected to operate in the number 10 role, while Julian Alvarez leads the line in the absence of Haaland.
As for Aston Villa, Unai Emery has made six alterations to the lineup that began the 2-0 victory over Wolverhampton Wanderers last weekend, with Clement Lenglet, Lucas Digne, Nicolo Zaniolo, Jhon Duran and Tim Iroegbunam all coming into the team - the latter is handed just his second Premier League start and first of the season.
Emiliano Martinez also misses out due to illness, with Robin Olsen starting in his place. Ezri Konsa and Diego Carlos are joined in defence by Lenglet and Digne, who are handed starts at the expense of Pau Torres and Alex Moreno, who drop to the bench.
Iroegbunam will link arms with ex-Man City man Douglas Luiz in centre-midfield as Zaniolo and Morgan Rogers operate out wide
Moussa Diaby, who has been involved in four goals (one goal, three assists) in his last four Premier League appearances, is joined in attack by Duran, who replaces injured top scorer Ollie Watkins.
Leon Bailey, who scored the only goal in a 1-0 victory over Man City in the reverse fixture four months ago, is among the Villa replacements.
Manchester City: Ortega; Lewis, Dias, Akanji, Gvardiol; Rodri, Bernardo; Doku, Foden, Grealish; Alvarez
Subs: Carson, Stones, Kovacic, Haaland, De Bruyne, Gomez, Nunes, Bobb, Susoho
Aston Villa: Olsen; Konsa, Carlos, Lenglet, Digne; Zaniolo, Iroegbunam, Luiz, Rogers; Diaby; Duran
Subs: Gauci, Chambers, Torres, Moreno, Bailey, Kesler-Hayden, Tielemans, Kellyman