Wenger accepts the loss of Arsenal's talisman - who has an outside chance of returning for the trip to Hull on Saturday - is a big blow.
However, the Gunners boss insists his side have the quality to nevertheless secure their place in the quarter-finals by overturning a 2-1 deficit from the first leg.
"Cesc has a hamstring problem and we could not even take a gamble with him," said Wenger.
"I was hoping he would recover after the Burnley game because we were cautious with him.
"We don't know how long he will be out. He is having a scan today and we are convinced it will only be a small time, and he has a small chance of getting back for next weekend against Hull, but to play him again [tomorrow] would mean significant damage."
Wenger, though, maintained: "Ideally we wanted him to be there, but we want to qualify and the absence of Cesc is no excuse at all.
"We have enough players and a strong enough squad to get round that and have enough chances to qualify."
Fabregas spent several weeks on the sidelines earlier this season because of a similar problem, yet remains Arsenal's leading scorer this season with 17 goals.
Wenger feels this latest fitness set-back is not about player burnout.
He said: "I cannot fault Spain, they only played him in one half [against France].
"Cesc has given a lot recently. It is a re-occurrence in the same hamstring so we have to find out why it creates some problems."
With Fabregas out, France international Samir Nasri could move into the centre of midfield, alongside Cameroon defensive midfielder Alex Song, whose domestic two-match ban does not apply in Europe.
Wenger feels the 22-year-old - who suffered a fractured leg in pre-season - has come a long way since arriving from Marseille during the summer of 2008.
"In the last few weeks he has got stronger and more confident," said the Arsenal boss.
"He is very versatile, can play defensive midfield, attacking midfield and on the flanks.
"We have a few players like that and I love that.
"Samir has adapted very quickly. He is a very intelligent boy, a quiet boy, he analyses what is happening on the pitch very quickly and has good technical potential."
Arsenal have not overturned a first-leg deficit in European competition since the UEFA Cup tie against Hajduk Split during the 1977-78 season. In the Champions League, the Gunners went out after an away defeat to Bayern Munich in 2004-05, lost to PSV Eindhoven in 2006-07 and exited the competition last season to Manchester United after being outplayed over both legs.
Wenger, though, maintains tomorrow will be different.
"This time, we have scored," said the Arsenal boss.
"When you lose 1-0 away from home it is a difficult game because when you start the next game you know it is almost over
because you have to score two or three goals to qualify.
"This time it is different - if we score one and do not concede then we will qualify."
Porto were thrashed 4-0 on their last visit to Emirates Stadium during September 2008 - the Dragon's worst away reverse in the competition.
Wenger feels that result will count for nothing when the Portuguese side return to north London on Tuesday.
He said: "I do not think anyone will be complacent.
"We know it will be a tricky game, but we believe we can do it.
"We have good confidence, we are in a good position, so let's go for it."
Arsenal 8/13, Draw 13/5, Porto 4/1