De Bruyne was taken off at half time in the Citizens' 0-0 Champions League draw with Inter Milan due to a groin issue, but Pep Guardiola stated at his pre-match press conference on Friday that the Belgian "could" be fit to feature versus the Gunners as he was 'feeling a little better'.
However, De Bruyne has not recovered in time to make the matchday squad and Guardiola has made a total of three changes to the side that drew with Inter, with Kyle Walker, Ilkay Gundogan and Jeremy Doku all coming in for De Bruyne, Rico Lewis and Jack Grealish.
Walker will captain Man City at right-back, joining Ruben Dias, Manuel Akanji and Josko Gvardiol in the back four, while Gundogan will link arms with Rodri in centre-midfield.
Bernardo Silva is set to operate in a central attacking role in the absence of De Bruyne, with Doku and Savinho playing out wide and star striker Erling Haaland, who has scored nine goals in just four league games, leading the line once again.
As for Arsenal, Mikel Arteta has made two changes to the side that played out a goalless stalemate with Atalanta BC in the Champions League on Thursday.
Ben White has been a first-team regular for the Gunners for some time, but he has been replaced in defence this afternoon by summer signing Riccardo Calafiori, who is handed his first Premier League start.
Calafiori is expected to start on the left side of a back four, with Jurrien Timber moving over to right-back as William Saliba and Gabriel Magalhaes continue at centre-back.
The other change made to Arteta's lineup sees Leandro Trossard come in for ex-Man City man Gabriel Jesus; the Belgian is set to start in the centre of a three-man frontline including Bukayo Saka and Gabriel Martinelli.
Arsenal's midfield is made up of Kai Havertz, Thomas Partey and Declan Rice, the latter is back in a Premier League XI after missing the 1-0 North London derby triumph over Tottenham Hotspur through suspension.
Manchester City starting lineup: Ederson; Walker, Akanji, Dias, Gvardiol; Rodri, Gundogan; Savinho, Bernardo, Doku; Haaland
Subs: Ortega, Carson, Stones, Kovacic, Grealish, Nunes, Foden, Lewis, McAtee
Arsenal starting lineup: Raya; Timber, Saliba, Gabriel, Calafiori; Havertz, Partey, Rice; Saka, Trossard, Martinelli
Subs: Neto, White, Kiwior, Kacurri, Lewis-Skelly, Jorginho, Nwaneri, Sterling, Jesus