The Citizens have lost Rico Lewis to suspension after his red card in the 2-2 draw with Crystal Palace last weekend, and the England international is likely to be one of six Citizens absentees for the visit of the Red Devils.
Rodri (ACL), Oscar Bobb (leg) and Nathan Ake (thigh) will play no part in this one either, and Guardiola should also be without John Stones (foot) and Manuel Akanji (unspecified) for the blockbuster battle.
As a result, the City boss will seemingly have no choice but to start either Jahmai Simpson-Pusey or Josh Wilson-Esbrand in defence, and the former looks the likeliest to get the nod on account of actually earning some senior minutes this term.
Simpson-Pusey's inclusion in the heart of defence should push Josko Gvardiol out to the left-hand side, but on a brighter note, Mateo Kovacic is back in the ranks and could step in for a leggy Ilkay Gundogan in midfield.
There is every chance that Kevin De Bruyne could drop deeper alongside Kovacic, allowing Phil Foden - who has struck six goals in his last four Premier League Manchester derbies - to occupy the number 10 position.
A recall could also await Matheus Nunes on the left-hand side, while Bernardo Silva should also support Erling Haaland, one goal or assist away from reaching 10 direct involvements against Man United in the top flight.
Manchester City possible starting lineup:
Ederson; Walker, Dias, Simpson-Pusey, Gvardiol; De Bruyne, Kovacic; Silva, Foden, Nunes; Haaland
Written by
Ben Knapton