Arsenal suffered a worsening of their Carabao Cup troubles when manager Mikel Arteta confirmed that Declan Rice, Noni Madueke, and Riccardo Calafiori are sidelined with injuries.
The three players were excluded from the squad for the fourth-round fixture against Fleetwood, which ended in a penalty shootout defeat.
Calafiori entered the match as a doubtful participant after experiencing difficulties near the conclusion of Saturday's 2-0 victory against Everton.
However, the absence of Madueke and Rice comes as an unexpected setback, particularly with Arsenal scheduled to visit Anfield to play Liverpool on Sunday.
Arteta, 44, stated: "Calafiori was out, Noni was out with an ankle [issue]. And Declan finished with a problem [against Everton] the other day. That's why I had to substitute him."
Fleetwood defeated the visitors despite the absence of several prominent squad members.
Arteta still managed to field a competitive lineup that featured Jurrien Timber, Kai Havertz, and Viktor Gyokeres.
Nevertheless, the League Two club eliminated them from the competition by prevailing in a tense penalty shootout.
Arteta added: "First of all, congratulations to Fleetwood for going through in the next round, in the manner they've done it, the atmosphere they have created, and, yeah, a really sad day for us."
Arteta commented: "I cannot fault at all the attitude of the players. I haven't seen anyone not doing what is required at this level."
He continued: "But, obviously, we insisted so much, we have so much of the ball, so many chances, so many shots. And if you want the margins to be bigger than going to penalties, obviously, you need to capitalise on that. And we didn't. And football is about that."