Sky sources close to the player understand he could be out for between two to four months.
The 27-year-old is currently undergoing tests to discover the full extent of the injury.
A statement released by City read: “Kevin De Bruyne is undergoing tests on his right knee after sustaining an injury at training on Wednesday.
“The extent of the problem is not yet known and we will bring you further updates on Kevin’s condition in due course.”
De Bruyne returned to Manchester City last week after being allowed extended time away from the squad following his involvement at the World Cup with Belgium.