Arsenal lost Granit Xhaka and Pablo Mari to injuries within the first 25 minutes of their Premier League return against Manchester City.
After Sheffield United earned a draw at Aston Villa in Wednesday's early kickoff, the Gunners and City met behind closed doors at a wet and rainy Etihad Stadium.
Xhaka was injured just seven minutes into the second match marking the resumption of the top-flight amid the coronavirus pandemic.
The midfielder went over on his ankle as he chased back in midfield, and after being assessed by Arsenal's medical team, he was deemed unfit to continue.
Xhaka's injury forced Mikel Arteta into a change just moments into the club's first match in three months, with the Spanish manager turning to Dani Ceballos to replace his injured midfielder.
With 21 minutes on the clock, the away side were dealt another major blow as Pablo Mari pulled up after being beaten by Kyle Walker, whose marauding run ended when his cut-back failed to find any of his City team-mates.
The 25-year-old centre-back, who is currently on loan at Emirates Stadium from Flamengo, was unable to shake off the issue and had to be substituted for David Luiz, leaving Arteta's game plan in tatters.
The Gunners were billed as underdogs heading into the contest, having slipped to ninth in the Premier League standings before play was stopped due to the coronavirus outbreak in March.
Arteta's men are 17 points behind the reigning Premier League champions at the moment, but they have yet to suffer a single top-flight defeat in 2020.
Arsenal will need to finish the season strongly to have any hope of securing a top-four finish, with Chelsea currently occupying the final Champions League spot.
City, meanwhile, look set to relinquish their domestic crown to runaway leaders Liverpool, having fallen 25 points off the pace with only ten fixtures left to play.
Pep Guardiola's men may also have a fight on their hands for the coveted runners-up position, with Leicester City hanging from their coattails in third after a brilliant first full campaign under Brendan Rodgers.