Mikel Arteta was handed a further selection problem with Arsenal back-up goalkeeper Mat Ryan out injured, as well as Kieran Tierney.
It comes after Bernd Leno was sent off against Wolves for denying a goalscoring opportunity on Tuesday night.
With the ball sprayed over the top of the Gunners defence, the German came flying out of his box.
But he cleared the danger using his hand, almost punching it out of play and referee Craig Pawson showed him a red card.
It came on a miserable night for Arsenal, who were already 2-1 down to Wolves at the time.
The north Londoners were a goal up through Nicolas Pepe before David Luiz was sent off on the cusp of half-time after being adjudged to have fouled Willian Jose in the box.
Ruben Neves scored from the penalty spot and Joao Moutinho netted a long-range effort shortly after half-time.
The result leaves Arsenal in 10th, though Aston Villa and Everton - the two teams directly above them - have three games in hand over them.
And Arsenal face Dean Smith's high-flying outfit next in a crucial clash at Villa Park on Saturday.
Arteta will not have either Luiz or Leno for the match, though in defence he has back-ups such as Gabriel Magalhaes and Pablo Mari.
But between the sticks, the Spaniard has a problem with second keeper Ryan injured.
Arteta said: "He had a muscular issue and in the last two days he hasn't been able to train. Hopefully, we can get him back in the next few days."
It will be a race against time for the Australian to be fit for the weekend, if not Runar Alex Runarsson will likely be deployed.
And it will be a huge test for the former Dijon star, who lost Arteta's confidence in the Europa League.
That directly resulted in Ryan's arrival in the January transfer window on loan from Brighton.
Tierney was already missing from the match against Wolves on Tuesday and it is notable how much the Gunners rely on the Scotsman.
It remains to be seen whether the former Celtic star will be fit for the weekend, though Arteta admitted no decision has been made yet.
When asked how close he was to making the line-up on Tuesday, the Spaniard said: "He wasn’t close at all hopefully in the next few days he feels much better."
Arteta revealed Arsenal will appeal Luiz's red card, though he did say there were no excuses for Leno's moment of madness.
"Sat here, I would say yes, let's go straight away," the Gunners coached said. "But we have to speak with legal and the club and make the decision what the best thing to do is.
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"I've seen the replay 10 times from five different angles, and I cannot see any contact. I would like to see if VAR have different angles.
“Bernd comes out and hits the ball with his hand, it's a clear red card and we're down to nine players and it's almost impossible to win."
Villa face West Ham tonight at home, with David Moyes' men in one of their best seasons in recent history as they sit fifth in the Premier League.
