City head south to the London Stadium as they look to pick up where they left off in the Premier League.
Guardiola suggested that the season truly starts now but admitted it was an advantage to go into the international break with four wins from four.
He has been without Kevin De Bruyne since the opening day of the season and will have neither John Stones nor Jack Grealish available for selection again on Saturday.
Mateo Kovacic also picked up a knock while away with Croatia and will be absent.
It leaves Guardiola with little choice on his first game back after undergoing emergency back surgery in Barcelona, and the City boss could make just one change from the side that thrashed Fulham 5-1.
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