Mbappe is suffering from a calf strain that saw him miss Saturday's 2-1 win over Lens which kept PSG in the Ligue 1 title race.
The absence of the French World Cup winner from the start is a huge blow to PSG's hopes of reaching the final for a second consecutive season.
City manager Pep Guardiola makes two changes from the side that started in Paris six days ago as the Premier League leaders aim to reach the final for the first time in their history.
Oleksandr Zinchenko and Fernandinho come in for Joao Cancelo and Rodri as Guardiola makes nine changes from the team that moved to the brink of a third English title in four years with a 2-0 win at Crystal Palace on Saturday.
Raheem Sterling is again relegated to the bench with Guardiola opting for a flexible front three of Phil Foden, Kevin De Bruyne and Riyad Mahrez.
Ederson; Kyle Walker, Ruben Dias, John Stones, Oleksandr Zinchenko; Ilkay Gundogan, Fernandinho (capt), Kevin De Bruyne; Riyad Mahrez, Bernardo Silva, Phil Foden
Coach: Pep Guardiola (ESP)
Paris Saint-Germain (4-2-3-1)
Keylor Navas; Alessandro Florenzi, Marquinhos (capt), Presnel Kimpembe, Abdou Diallo; Leandro Paredes, Ander Herrera; Angel Di Maria, Marco Verratti, Neymar; Mauro Icardi
Coach: Mauricio Pochettino (ARG)
Referee: Bjorn Kuipers (NED)