Arsenal have confirmed Pablo Mari has suffered a "significant" ankle injury, while Granit Xhaka will be out of action for at least two weeks.
Midfielder Xhaka collided with team-mate Matteo Guendouzi and had to be replaced by Dani Ceballos just eight minutes into the Gunners' 3-0 Premier League defeat at Manchester City on Wednesday.
Mari pulled up after chasing City full-back Kyle Walker and went off for David Luiz, who endued a nightmare performance at the Etihad Stadium.
On Friday, Arsenal confirmed Xhaka has sprained his right ankle and should be back in training in a fortnight.
Mari, however, is undergoing further specialist treatment due to damage to his left ankle.
The news is a blow to Mikel Arteta, who is already without a number of first-team players.
Calum Chambers is not expected to play again in 2019-20 as he recovers from an anterior cruciate ligament tear suffered in December, while Sokratis Papastathopoulos is sidelined for up to two weeks with a thigh strain.
Cedric Soares will not resume training until at least end of June, compounding Arsenal's defensive problems.
Midfielder Lucas Torreira, meanwhile, is still recovering from an ankle fracture and is not expected to be back until July.
Arteta's side are ninth in the Premier League with nine games remaining, eight points adrift of the top four.