Arsenal lost England pair Alex Oxlade-Chamberlain and Theo Walcott to injury during their 3-0 League Cup fourth-round loss at second-tier Sheffield Wednesday on Tuesday.
Oxlade-Chamberlain, one of only three Arsenal players to keep their places from Saturday's 2-1 win over Everton, went off in the fifth minute at Hillsborough after going down with an unspecified injury.
He was replaced by Walcott, but the substitute lasted only 13 minutes himself before being forced off by what appeared to be a calf problem, with 17-year-old midfielder Ismael Bennacer coming on for his debut.
"We are short now because we lose Chamberlain today, we lose Walcott and we have already a few injuries," Arsenal manager Arsene Wenger told Sky Sports.
"It is a big blow for us, of course to lose the game, but even more for the other competitions, which are very important for us, to lose two players of that stature."
Oxlade-Chamberlain and Walcott's injuries occurred less than a week after Welsh midfielder Aaron Ramsey was ruled out for up to a month with a hamstring injury.
Second-choice goalkeeper David Ospina, club captain Mikel Arteta, midfielders Jack Wilshere and Tomas Rosicky and forward Danny Welbeck are also currently sidelined.