The Belgium international is also a doubt for the Premier League game against West Brom on Saturday after he was injured and taken off at half-time in Sunday’s 1-1 draw with Southampton.
Pablo Zabaleta is also ruled out after he got a cut that required stitches in the defeat to Barcelona but Vincent Kompany is expected to be in the squad after playing 78 minutes on Sunday.
City boss Pep Guardiola told a news conference: “Kevin has a knock and he cannot play. Pablo I think cannot. Vincent I think he can but I need to see training and regeneration.”
Guardiola said he is “going to rotate” for the derby because of a hectic schedule that sees City play seven games in 21 days.
“Some of them will play, first because they deserve it and second because we played tough, tough games,” he told a news conference. “We play 35 minutes with 10 men against Barcelona and it was a tough game against Southampton.
“People are tired. I need today to see the players in the training session and after I am going to decide but I’m pretty sure we’re going to rotate.”
Academy products Aleix Garcia, Angelino, Brahim Diaz, Tosin Adarabioyo, Angus Gunn and Pablo Maffeo were all in the 18-man matchday squad for the win over Swansea City.