City have accumulated six points from their opening three League Phase fixtures under Enzo Maresca, who will still be reeling after the 1-0 loss to Brighton over the weekend.
Leipzig have picked up just three points from their first three matches, leaving them down in 29th place in the 36-team League Phase table.
City are the clear favourites, and after the defeat to Brighton, the side will come out fighting against the German side, who have struggled under manager Martin Demichelis.
Man City vs RB Leipzig team news
For Leipzig, Assan Ouedraogo (shoulder) and Marc Guiu (muscle) remain sidelined with injuries, whilst Maxime Esteve is doubtful with a knock.
City are without Antoine Semenyo in what is a relatively injury-free squad.
Man City vs RB Leipzig predicted line-ups
RB Leipzig: Vandevoordt; Baku, Orban, Lukeba, Raum; Seiwald, El Aynaoui; Gruda, Nkunku, Nusa; Romulo.
Manchester City: Donnarumma; Lewis, Khusanov, Dias, Gvardiol; Anderson, Fernandez; Foden, Cherki, Ndiaye; Haaland.
Man City vs RB Leipzig kick-off time
Both sides meet at the Red Bull Arena for a 20:00 kick-off, UK time.
Form
Man City: LDLWW
RB Leipzig: WWLWW
Key stats
City have won 4 of the 6 previous meetings, with 1 draw and 1 Leipzig victory and have won 21 of 32 Champions League matches against German opposition.
Leipzig have lost their last five European matches against English clubs and conceded 10 goals across their heavy defeats to Bayern Munich and Real Madrid.