The Spain playmaker, who scored the late winner in the Premier League leaders' victory over West Ham on Sunday, is being rested for the Group F game in Kharkiv.
Kevin De Bruyne was also absent from the squad which left Manchester on Monday afternoon as he is suspended for the game on Wednesday evening.
Both players will be expected to return for the derby clash with Manchester United at Old Trafford on Sunday, and Silva is clearly being rested with that game in mind.
The only other notable omissions from the travelling party were injured defenders Benjamin Mendy and John Stones.
Youngsters Phil Foden, Brahim Diaz, Tosin Adarabioyo and Daniel Grimshaw were included by manager Pep Guardiola and look set to figure at some point.
City are already assured of top spot in the group having won their opening five matches.