The Denmark defender missed the midweek Champions League clash with Porto and has failed to recover in time for the Wembley showdown.
N’Golo Kante is fit enough to start his second match in a week, with Mateo Kovacic still sidelined through hamstring trouble.
City will be without record goalscorer Sergio Aguero once again.
The Argentinian has missed the last three games with a muscular problem, the latest in a catalogue of fitness issues to have marred his final season at the club.
City have no other fresh fitness concerns but, as in previous domestic cup ties this season, Zack Steffen could take over from Ederson in goal.
Chelsea provisional squad: Arrizabalaga, Rudiger, Alonso, Jorginho, Silva, Kante, Abraham, Pulisic, Werner, Caballero, Zouma, Mendy, Giroud, Mount, Hudson-Odoi, Chilwell, Ziyech, James, Azpilicueta, Havertz, Palmieri, Gilmour.
Manchester City provisional squad: Steffen, Ederson, Walker, Cancelo, Stones, Dias, Laporte, Garcia, Ake, Zinchenko, Mendy, Rodri, Fernandinho, Gundogan, De Bruyne, Silva, Foden, Torres, Sterling, Mahrez, Jesus.