GWS midfielder Adam Kennedy and All-Australian defender Sam Taylor have been sidelined with long-term injuries in a huge double-blow for Adam Kingsley's side.
Kennedy will miss the rest of the season because of a torn anterior cruciate ligament, while a serious hamstring injury has put Taylor out of acton for the next 10 weeks.
The players suffered their injuries during Saturday's 21-point loss to Brisbane in Canberra.
Taylor was substituted out of the match during the third quarter with what scans revealed is a grade-three hamstring strain.
"Unfortunately Sam will miss around 10 weeks with this hamstring injury," Giants football boss Jason McCartney said in a statement.
"It's frustrating for Sam, who has been in exceptional form, but we look forward to welcoming him back after our mid-season bye."
Inaugural Giants player Kennedy will undergo a knee reconstruction after landing awkwardly in a contest for the ball against the Lions.
"It's shattering news for Adam and the club but we'll wrap our arms around 'Kenners' and give him all the support he needs," McCartney said.
"He's a much-loved member of our footy club and we know he'll attack this setback with his trademark hard work and diligence."
GWS forward Daniel Lloyd was a late withdrawal from the Brisbane clash with a calf issue.
He faces a fitness test ahead of Saturday's derby clash with Sydney at the SCG.
