The England centre-back was unavailable for the midweek Champions League semi-final defeat to Real Madrid, creating a defensive problem that only got worse when Kyle Walker was forced out with an ankle injury.
Kyle Walker is also absent, meaning Joao Cancelo and Oleksandr Zinchenko are operating as full-backs.
With only the Premier League title left to fight for, Guardiola can at least put all his energy into defending this crown, unlike Liverpool, who have to focus at least partially on their upcoming FA Cup and Champions League final after being detained by Tottenham yesterday.
Raheem Sterling and Jack Grealish team up with Gabriel Jesus on the attack.
Guardiola reassured fans during his press conference on Friday that Kevin De Bruyne would be fit to face Newcastle, with his substitution in Spain for “tactical” reasons.
Starting Man City XI (4-3-3): Ederson; Cancelo, Laporte, Ake, Zinchenko; Gundogan, Rodri, De Bruyne; Mahrez, Sterling, Grealish.