The Spaniard's return is one of three changes from the side that drew 1-1 with Newcastle United on Tuesday.
Nicolas Otamendi has returned to the back four, replacing captain Vincent Kompany, who is not in today's squad, while Kelechi Iheanacho has been given the nod to start up front alongside Sergio Aguero.
Stoke boss Mark Hughes has also made three changes to his side who were beaten 4-0 by Tottenham Hotspur on Monday.
Afellay is likely to face a significant spell on the sidelines after suffering a "serious" knee injury in training.
Manchester City: Hart; Zabaleta, Mangala, Otamendi, Kolarov; Navas, Toure, Fernando, Silva; Iheanacho, Aguero
Subs: Caballero, Demichelis, Clichy, De Bruyne, Delph, Bony, Sterling
Stoke City: Given; Muniesa, Wollscheid, Shawcross, Bardsley; Whelan, Cameron; Arnautovic, Imbula, Diouf; Joselu
Subs: Haugaard, Adam, Teixeira, Crouch, Bojan, Choulay, Shenton
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