England's John Stones, Kyle Walker, Raheem Sterling and Phil Foden will all be absent, while Rodri and Ferran Torres are unlikely to be involved despite returning to training on Wednesday.
Kevin De Bruyne, Ederson and Gabriel Jesus are also unavailable, but a strong XI should still include the likes of Joao Cancelo, Ruben Dias, Fernandinho, Ilkay Gundogan, Bernardo Silva and Riyad Mahrez.
Man City are on the verge of completing a deal for Jack Grealish, meaning that there is a chance that he could make the squad for Saturday's clash at Wembley.
The absence of a number of senior players will naturally open the door for youngsters to impress, and Sam Edozie, who has recently been praised by head coach Pep Guardiola, could potentially feature in the final third of the field alongside Mahrez and Bernardo.
Cole Palmer is also being tipped to feature as part of a midfield three, with the 19-year-old making a positive impression during the team's preparations for the new campaign.
Zack Steffen, meanwhile, has been involved in Man City's pre-season and is expected to get the nod between the sticks due to the absence of number one Ederson.
Man City possible starting lineup: Steffen; Cancelo, Dias, Ake, Mendy; Fernandinho, Gundogan, Palmer; Mahrez, B Silva, Edozie