Robin van Persie will miss Arsenal's Champions League round of 16, second leg clash with Barcelona on March 8, the club confirmed this afternoon.
Van Persie has been ruled out for at least three weeks after sustaining the injury in Sunday's Carling Cup final defeat by Birmingham.
However, Arsene Wenger described Cesc Fabregas as a "possible" for the Nou Camp trip after revealing he is making quick progress in his rehabilitation from a hamstring problem.
Losing Van Persie is a seismic blow to Arsenal's hopes of staging another upset against the Spanish champions.
The in-form 27-year-old Holland striker sustained the injury in the act of scoring Arsenal's equaliser during the 2-1 defeat at Wembley.
The goal was his 13th in 11 games - a haul that includes the equaliser against Barcelona in the first leg, which the Gunners edged 2-1.
"Unfortunately, we had bad news on the scan and he will be out for the next three weeks for sure," Wenger told Arsenal TV Online.
"It could be longer. The shortest delay we can imagine is three weeks, so he is definitely out for Barcelona."
The loss of Van Persie has been slightly tempered by the encouraging update on Fabregas' fitness.
The Spain midfielder sustained his hamstring problem against Stoke last Wednesday but has responded well to treatment.
He will definitely miss tomorrow's FA Cup fifth-round replay against Leyton Orient and Saturday's Barclays Premier League showdown with Sunderland, but could return for Barcelona.
"Cesc is looking possible [for that game]. He is making quick and good progress. It is possible," said Wenger.
Theo Walcott, who had already been ruled out against Barcelona, remains a fortnight away from recovering from his sprained ankle.
"He is out. We said from the day he got the injury against Stoke you could count three weeks," said Wenger.
Alex Song incurred a knee problem against Birmingham and will miss the tie against Orient tomorrow, but should return against Barcelona.
Laurent Koscielny is nursing a minor hamstring problem and will be rested for the replay
Manuel Almunia will start in goal with Wojciech Szczesny on the bench and midfielder Abou Diaby is expected to feature.
"Alex Song has a knee problem. From his scan we had good news, it is only blood from a kick on the outside of his knee," said Wenger.
"He is out for Leyton Orient and has a very small chance for Saturday. But he has a good chance for Barcelona.
"Koscielny has a tight hamstring. There is a little bit of fatigue in there as well so we will give him a breather.
"Almunia needs games so he will play, but Wojciech is all right and will be on the bench.
"Diaby was not in the squad on Sunday. I was cautious with him.
"He has missed many games this season and I did not want to take a gamble with the intensity of a cup final. He will play tomorrow night."