De Bruyne has faced an intense 12 months, having been outstanding for City as it accrued 100 points to win last season’s Premier League title before helping Belgium to finish third in Russia, The Independent reported.
He only returned to training at City on Monday of last week, playing for the final half-an-hour last Sunday as Guardiola’s side began its league season with a 2-0 victory at Arsenal.
However, he then suffered a knee injury in training on Wednesday.
Guardiola expects De Bruyne to be fit again by the beginning of December, but acknowledges that City will have a tough task dealing with his absence, just as the Citizens did when a knee injury ruled out left-back Benjamin Mendy for virtually the whole of last season.
The City manager said, “We never know. My opinion is that when you ask a lot of the players, over more than 11 months, then after he comes back, this [injury] can happen.
“I don’t know the reason why. Nobody knows, but I’m pretty sure this can influence it. When you are fresh here, fresh on your legs, it doesn't happen. Sometimes it can.
“It’s part of the game for the players – it’s normal, they don't rest. It’s a tough season, with short recovery times. They [the football authorities] say ‘let’s go’ and we are in the competition. Human beings have a limit and sometimes these things happen.
“My advice to him now is to rest, take the holidays he didn’t get in these two or three weeks, do it now. Then he’ll start training and we'll be waiting for him with big arms.”
De Bruyne’s absence is set to give David Silva more opportunities to impress, with the Spain playmaker free to commit himself to club duties after announcing his international retirement on Monday.
Silva missed several matches last season to spend time with his son Mateo, who was seriously ill in hospital after being born prematurely. Mateo was allowed to leave hospital in May, five months after being born, and his now recovering well.
Guardiola said, “I’m glad for him. If he has decided to do that, it is because he feels it is the right moment. Congratulations to him.
“He has played more than 100 games, winning two European Championships and one World Cup. He is one of the most fascinating, incredible players in the whole history of Spain.
“He decided. No one at Man City, and not myself, pushed him. The player has to feel it. He decided to rest a little bit more with his wife and his little boy, and play with us.”