The midfielder damaged the lateral collateral ligament (LCL) in his right knee during a training session on Wednesday.
Riyad Mahrez, Bernardo Silva and Raheem Sterling played behind Sergio Aguero as De Bruyne came on as a 60th-minute substitute during the defending Premier League champions’ 2-0 win at Arsenal last weekend.
De Bruyne, City’s Player of the Year last season, had only returned to the club last week after being allowed extended time away from the squad following his involvement at the World Cup with Belgium.
The former Chelsea and Wolfsburg midfielder missed more than two months of the 2015-16 season after injuring his knee against Everton in a League Cup tie at the Etihad.
Manchester City host Huddersfield in their first home fixture of the 2018-19 season on Sunday.
De Bruyne’s injury can provide a platform for England’s U21 international Phil Foden to flourish.
“I don’t think Pep Guardiola would have any problem with starting him against Huddersfield with there being little danger of them losing that game,” said Le Tissier, who believes Foden should now be getting 10-12 starts a season.
“There’s a lot of competition at City and he’s going to have to fight hard but, in the long term, that will beneficial to him and England because if he does break through then he is going to have the experience of playing with the best players at the highest level.”