Kevin De Bruyne suffered knee ligament damage in his left knee during Thursday night’s Carabao Cup fourth-round win over Fulham.
De Bruyne underwent scans on Friday at the CFA and will undergo no surgery but he is expected to be out for between 5-6 weeks.
The 27 year old, De Bruyne will miss Sunday’s clash with Southampton, Wednesday’s Champions League game with Shakhtar Donetsk and the derby with United.
Belgium will also be without the former Chelsea midfielder when they face Iceland and Switzerland in the UEFA Nations League games during the international break.
On whether De Bruyne’s injury setback could have been prevented, Guardiola said: “No, I don’t think so,” during his post match interview.
“Football is football, it was dynamic game with a lot of contact and this sometimes happens.”
“Kevin De Bruyne is out and we are sad for him, nobody likes to have injured players but he will come back to the player he is and he will be fine.
“Unfortunately he is injured, but fortunately he does not need surgery. In between four and six weeks the doctor said he will come back.
“De Bruyne was out for two and a half months, we are sad for him. When you come back [from injury] you cannot expect on day one he will be the player we know he is.”
“He (De Bruyne) needs time to settle and take the rhythm, pace, everything. Yesterday he came back but it is what it is.”
The 27-year-old had missed two months of the season after damaging ligaments in his right knee during training in August.