Granit Xhaka has been ruled out for three months with a significant injury to his medial knee ligament.
The Arsenal midfielder suffered the injury in the Gunners' 3-1 North London derby victory over Tottenham Hotspur on Sunday but will not require surgery.
Xhaka had only made four Premier League appearances for Arsenal this season, being ruled out through suspension and a Covid-19 diagnosis.
The Switzerland captain has been integral to Mikel Arteta 's reign, making 31 top-flight appearances last term.
But now the Spanish manager will be without the 29-year-old, who was close to joining Jose Mourinho at Roma during the summer transfer window.
Instead, Xhaka agreed to a new four-year deal at the Emirates.
On Sunday, he started his first game since August 28 when he was sent off and subsequently banned for three matches against Manchester City.
Regarding the decision to put him back into the starting XI, Arteta said: "Obviously we had to think about it, we had different options to play against them.
"We believed that the way they set up and what we wanted to do in the game, it was the right call to do that," he explained.
"I understand that a lot of people will say, ‘You won the last two games, why change it?’ but we did it with the intention that it was the right thing to do to start the game and then change it, and unfortunately he got injured.
Arteta added on the issue before learning the full extent: "I'm pretty worried because it doesn’t look very positive at the moment."
The Arsenal manager told talkSPORT in August after confirming he would stay in North London: "He is a key member of our squad."
He went on to say later that month: "We never wanted to let him go. We explained to him the role he would have in the team, how important he was and how far he has come in the last two seasons.
"And the fact that he has come through some difficult moments and how he has reacted and achieved and the respect he has gained, not only on the field, but around the club and in that dressing room," Arteta continued.
"We believe that he was a really important figure and we need players like that for the development of the young players we have. It’s difficult because you don’t get to see much of what happens inside.
"People just analyse a performance or a way of a player playing and whether you like him more or less. But from our side there is no doubting his importance in the team and squad."
