Gloucester's Albert Tuisue, Val Rapava-Ruskin and Giorgi Kveseladze have been ruled out for the rest of the season because of injury.
Prop Rapava-Ruskin is to have surgery on a knee problem after the 30-year-old impressed in 16 appearances this term.
Georgia centre Kveseladze, 25, injured a hamstring while on international duty this month.
"We've been hugely unfortunate this season with the injuries we've sustained and losing three more players in such a short space of time is another significant blow to the squad," Gloucester chief operating officer Alex Brown told the club website.
"Albert, Val and Giorgi have all played key parts in our season and they're equally disappointed to be ruled out for the remainder of the 2022-23 campaign.
"They've all already started their respective returns with our on-site medical team, and we're wishing them all a speedy recovery."