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
Cherkasi 
Shakhtar Donetsk 
Spartak Moscow 
FK Makhachkala 
Nimes 
Bordeaux 
VFL Wolfsburg 
RB Leipzig 
Udinese 
AC Milan 
Valencia 
Sevilla 
Orenburg 
CSKA Moscow 
Kryvbas Kryvyi Rih 
Dynamo Kyiv 
Manchester City 
Crystal Palace 
Celtic 
Kilmarnock 
Bayer Leverkusen 
Union Berlin 
Brighton 
Leicester 
Nottingham Forest 
Everton 
Rubin 
Lokomotiv Moscow 
Fortuna Sittard 
Feyenoord 
Monaco 
Marseille 
Sampdoria 
Cittadella 
ST Malo 
Inter 
Cagliari 
Arsenal 
Brentford 
Bayern Munich 
Borussia Dortmund 
Celta Vigo 
Espanyol 
Ajaccio 
PSV 
Almere City FC 
Juventus 
Lecce 
Leganes 
Barcelona 
Casa Pia 
FC Porto 
Aberdeen 
Rangers 
Heracles 
AZ Alkmaar 
Chelsea 
Ipswich