Ederson, who has been heavily linked with a move to Saudi Arabia, missed the Citizens' 4-2 friendly win over Chelsea last weekend, with Guardiola stating after the match that the Brazilian was left out due to some "niggles".
The 31-year-old has subsequently emerged as a doubt, so Stefan Ortega could therefore be given the nod to play between the sticks at Wembley, as he did 12 months ago in Man City's penalty-shootout loss to Arsenal.
Ederson may not be the only high-profile absentee for Man City, as Euro 2024 finalists Rodri, Phil Foden, Kyle Walker and John Stones are yet to report back to first-team training and will seemingly not be ready in time to feature against Man United, while left-back Josh Wilson-Esbrand is set to miss out after coming off against Chelsea with a hamstring injury.
However, a host of senior star have returned to Guardiola's squad this week including Kevin De Bruyne, Bernardo Silva, Jeremy Doku, Ruben Dias, Manuel Akanji, Matheus Nunes and summer signing Savio, who could all be involved in some capacity on Saturday.
Erling Haaland was suffering with a minor muscle issue towards the end of last month, but he was fit to start and score a hat-trick in City's friendly win over Chelsea last time out and the Norwegian striker is expected to lead the line once again.
Manchester City possible starting lineup: Ortega; Lewis, Dias, Akanji, Gvardiol; Kovacic, De Bruyne; Bobb, Bernardo, Grealish; Haaland