The Gunners were already sweating on the fitness of captain Thomas Vermaelen's ankle injury before the players left for international duty, where fellow centre-half Laurent Koscielny limped off during France's defeat to Germany in Paris with a reported calf problem.
Should both men fail to recover in time for the trip to the Stadium of Light, then out-of-favour Sebastien Squillaci or Spanish 20-year-old Ignasi Miquel could have to step in to the heart of the defence alongside Per Mertesacker.
Francis Coquelin is another option, but the defensive-midfielder has missed a couple of matches with a hamstring strain.
Meanwhile, midfielders Tomas Rosicky (virus) and Aaron Ramsey, who returned from Wales camp with a calf injury, are also doubtful for the trip to the north-east.
Forward Gervinho is set to rejoin the squad following Ivory Coast's elimination from the African Nations Cup, but is expected to be given some recovery time before being thrown straight back into action as Arsenal look to maintain momentum from their four-match unbeaten run.
Nacho Monreal impressed on his debut after a deadline day move from Malaga.
The Spain international looks set for a run in the side with England left-back Kieran Gibbs still sidelined by a thigh problem.
It is another setback for the 23-year-old, who has suffered a string of fitness issues in recent seasons, including breaking his metatarsal in a Champions League game against Standard Liege in November 2009.
Gibbs, however, will not let that hold him back.
Speaking to the official Arsenal magazine in an interview conducted before his latest injury in the 2-2 draw against Liverpool, Gibbs revealed his positive attitude to spells on the sidelines.
He said: "Before that I had never really had injuries, but in the next couple of years I had quite a few and it was really frustrating.
"I did my knee and rolled my ankle, and later on I had a hernia.
"However, I just got on with it and never really listened to any comments.
"I just knew the most important thing was that I got back and let people judge me on my football."
Vermaelen, meanwhile, revealed he has taken inspiration from David Beckham's recent visit to Arsenal, where the former England captain trained ahead of his deadline day move to Paris St Germain.
"I didn't meet him for long, but I could tell straightaway that he's a very nice guy and a fantastic professional," Vermaelen wrote in the Arsenal matchday programme.
"That was obvious in a single day - he was working after the session, doing drills and keeping himself fit, and you have to give him a lot of credit for being in such good shape at the age of 37.
"It is not easy to get to the top and stay there as he has done - you have to work really hard every single day, and if young players can see that then it is an inspiration for them.
"Training with him was a special moment for me, too. Like Beckham, I certainly want to play football for as long as I can - it's partly about how your body feels, and about luck too, but in my opinion football is the best career there is so you want to enjoy it to the maximum."