Arsenal's torrid week continued on Friday when Arsene Wenger revealed that Per Mertesacker has been ruled out 'long term'.
Adding to Wenger's defensive problems is that Laurent Koscielny is also missing for Saturday's FA Cup fifth-round tie at Sunderland because of a knee problem.
But while Koscielny should recover in a week from the injury sustained during Wednesday night's painful 4-0 drubbing by AC Milan, Mertesacker may have played his last game this season.
The German international suffered ankle ligament damage during Saturday's Barclays Premier League victory against Sunderland that requited ankle surgery.
"Unfortunately he has had surgery and we have lost him for a while," Wenger told the club's official website, www.arsenal.com.
"How long I don't know. He had reconstruction of his ligaments, so it will be long term."
Koscielny limped off shortly before half time at the San Siro, but the prognosis on his injury is far more encouraging.
"He had a scan yesterday and the news is quite good," said Wenger. "He will be out for hopefully around a week.
He will miss the Sunderland game, but he should be back for next week." Wenger is facing a headache at centre-back with Mertesacker and Koscielny unavailable for the trip to the Stadium of Light.
Thomas Vermaelen's lack of match sharpness was exposed during Arsenal's heaviest European defeat, while Johan Djourou was far from impressive.
Sebastien Squillaci has been frozen out of the first team picture, but Alex Song can play centre-back if required.
Gervinho has finished international duty at the African Nations Cup and is included in the squad and defender Carl Jenkinson will soon return to training following his back problem.
Wenger also revealed that Kieran Gibbs suffered no setback at the San Siro after being out since October with a groin problem.
"Kieran played his first game in four months in Milan so of course it was a shock to go back to that level. But physically he's all right," said Wenger.
"Carl's back in full training on Monday. That's good news for us."
Djourou has urged Arsenal to atone for last season's Carling Cup final loss to Birmingham by winning the last piece of silverware available to them this season.
"This is a big opportunity for us. The FA Cup is one of the main targets and we have to go for it," he told Arsenal Player.
"Last season's League Cup final defeat is very motivating because we were very disappointed about what happened last time at Wembley and we want to put that right.
"I think it is something still in our heads, and it is difficult to swallow. We know if we can get to the final we can lift the trophy."
Martin O'Neill is hoping his Sunderland side can intensify Arsenal's pain - but has warned unhappy Gunners fans that under-pressure Wenger is the greatest manager the club has ever had.
The Sunderland boss, who has crossed swords with Wenger on the touchline in the past, insists his opposite number should not be condemned for the midweek 4-0 pasting by AC Milan in the first leg of their Champions League last-16 tie
The FA Cup now looks Arsenal's only chance of ending their seven-year trophy drought his season, but O'Neill believes his players can reverse the result of last weekend when the two sides met at the Stadium of Light and the visitors won 2-1.
O'Neill said: "The Milan defeat has been heavy for them and I think they would admit that and that it was something they didn't expect.
"AC Milan played very, very well indeed and Arsenal on the night didn't do so. Regardless of that I think their concentration will be on the FA Cup tie as it's a competition they have won reasonably recently and believe they can win.
"AC Milan are a top-quality team and, let's face it, we are not as good as AC Milan. They are playing in the last 16 of the Champions League and that's where every single football club worth its salt is aspiring to get to and we are a long way off that.
"That doesn't mean we are not capable of winning the match, and that we don't have one or two players who can definitely cause them problems.
I am just hoping that the advantages we might take into the game, such as having had an extra rest this week and playing at home, will help us."
Midfielder Lee Cattermole could be back in the Sunderland squad after recovering from a hamstring injury.
Nicklas Bendtner is back in training but, as the Denmark striker is on loan from the Gunners, he is ineligible for the fifth-round clash at the Stadium of Light. David Vaughan (ankle) is still out as are Wes Brown (knee) and Titus Bramble (Achilles/calf).
Sunderland V Arsenal - view commentary, squad, and statictics of the game live.