The reigning premiers were stung by losing important trio Harris Andrews (three matches), Darcy Gardiner (one) and Zac Bailey (one) to suspensions out of the season-opening defeat to the Western Bulldogs.
Hugh McCluggage went down with a calf strain and the Lions were dealt a further blow when young key forward Logan Morris, who kicked three goals against the Dogs, was ruled out of Saturday night's trip to the SCG with a fractured hand.
It will be the first time dual premiership coach Chris Fagan - now in his 10th season at the helm - will lead Brisbane with both Andrews and McCluggage out of the team.
"The good thing about us is there's a lot of great depth and a lot of players ready to go," Lions forward Kai Lohmann said on Thursday.
"We have players that can come in and play a role and hopefully the boys that come in can do a good job.
"I'm really excited for those boys to get an opportunity."
Former Essendon ruck Sam Draper is fit to play his first game for Brisbane against the Swans, after overcoming his achilles injury and foot stress reaction.
Lions Academy product Daniel Annable is set to debut after he was taken with pick No.6 in last year's draft, while McCarthy will play his first game since May 2024.
The 32-year-old missed Brisbane's back-to-back premierships with successive serious knee injuries.
"He's been pretty unlucky with injury, so it'd be a huge lift," Lohmann said of McCarthy's return.
"He's a cult hero at the club."
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