City face a United side in poor form while they themselves have won 10 league games in a row, but they will also be wary of a backlash from the hosts following their 4-0 drubbing at Everton on Sunday.
Here, Sports Mole looks at how City could line up for the must-win showdown at the home of their greatest rivals.
Guardiola confirmed in his pre-match press conference that Kevin De Bruyne will miss this game with the hamstring injury he sustained during the weekend win over Tottenham Hotspur.
City have a ready-made replacement in David Silva, who was dropped to the bench against Spurs, but Guardiola must also decide whether to keep faith with Phil Foden, who scored the only goal of the game at the Etihad.
Fernandinho is expected to come back into the team, which would in turn free Ilkay Gundogan up to play in a more attacking midfield role, while PFA Player of the Year contender Bernardo Silva could also drop deeper if required.
Benjamin Mendy will hope to regain his starting spot at left-back, while Guardiola could be tempted to include the experience of Vincent Kompany in defence, with the Man City skipper having led by example in many previous derbies.