West Coast star Harley Reid's season is over due to an ankle injury, while hamstrung Adelaide defender Max Michalanney is unlikely to return before the finals.
Reid will be joined on the sidelines by fellow young gun Bo Allan after the pair both suffered similar low-grade syndesmosis injuries.
Former No.1 draft pick Reid had to be helped off the field after damaging his right ankle in a tackle in the Eagles' 49-point loss to Fremantle on Saturday.
Allan suffered his season-ending injury after his foot was also caught in a tackle at training last Thursday.
The Eagles will at least hope key defender Harry Edwards will be able to return for their match against a wounded Melbourne outfit after being ruled out late against the Dockers with hamstring soreness.
Meanwhile, Michalanney - a crucial part of Adelaide's backline - was substituted out during the third quarter of Saturday night's thumping win over Port Adelaide and will miss four to six weeks.
It means the Crows will continue their push for a top-two berth without the versatile defender, who will need to prove his fitness for the finals.
“It’s unfortunate for Max given the season he’s been having,” Crows high performance boss Darren Burgess said.
“Thankfully for us, we know he’s an extremely diligent worker and will do everything possible to return stronger.”
Michalanney, 21, had played 64 of a possible 65 games since his debut in 2023.
Adelaide will miss Michalanney against Hawthorn's dynamic forward line on Friday night, while he will also be sidelined for games against West Coast, Collingwood and North Melbourne.
The Crows (56 points), sit second behind Collingwood (60) and just ahead of Brisbane (54).
Geelong, Hawthorn, GWS and Fremantle (all 52 points) are all jostling for top-four berths.
