"Unfortunately Kevin got a positive COVID test in Belgium and needs ten days," manager Pep Guardiola said at a news conference.
The 30-year-old Belgium midfielder cannot play Sunday against Everton in the English Premier League due to isolation.
He will also remain sidelined for next week's UEFA Champions League group match against Paris Saint-Germain.
De Bruyne scored against Wales in a 2022 FIFA World Cup qualifiers match in Cardiff that ended 1-1 on Nov. 16.
The Belgian national football team won Group E to book their place in Qatar 2022.
