Aguero had been self-isolating after being in close contact with another confirmed case, and has now talso returned a positive test result.
It is unlikely the striker would have played should he have received the all-clear, meaning Gabriel Jesus should lead the line.
Ferran Torres will be hoping for another chance to impress after finding minutes hard to come by of late, while Riyad Mahrez is another struggling for starts.
Kevin De Bruyne, who was removed before the hour mark against Aston Villa last time out, Phil Foden and Ilkay Gundogan will all likely be rested.
Zack Steffen should take his place in goal for the cup, while fellow youngsters Tommy Doyle, Taylor Harwood-Bellis and Cole Palmer may also be afforded time.
Predicted Manchester City XI (4-3-3): Steffen, Walker, Harwood-Bellis, Laporte, Mendy, Doyle, Fernandinho, Bernardo, Torres, Jesus, Mahrez