Sam De Koning will miss out on Geelong captain Patrick Dangerfield's 350-game milestone match after damaging his left shoulder.
The Cats defender will need surgery to repair an AC joint injury he suffered in their 95-point thumping of Essendon.
De Koning was substituted out of Saturday's game in the third quarter at the MCG after a ground ball contest with Bombers midfielder Will Setterfield.
The 24-year-old is expected to miss four to five weeks.
Geelong teammate Zach Guthrie is backing the depth in their defensive stocks as they look to extend to mark Dangerfield's milestone with a win against the third-placed Brisbane Lions (9-4-1).
The Cats (10-4) are second on the ladder and boast a five-game winning streak.
Star utility Mark Blicavs was deployed in De Koning's role against Essendon, while Guthrie has pointed to youngster Connor O'Sullivan as another option.
"Sam is a really important player for us. He's one that we really depend on every week to play on those taller types," Guthrie said on Monday.
"He's been doing a really good job for us but we've got a number of guys who can roll through that position."
Guthrie's brother Cam has suffered another setback in his return to AFL.
The older Guthrie, after having surgery on his left achilles in February, was forced to sit out of a VFL game last week with a calf complaint.
The 32-year-old onballer has not featured at AFL level this year and has played just ten games in the last two seasons.
But Zach Guthrie, 26, remains confident his brother's return is imminent.
"He ended up missing the VFL game on the weekend, just to hopefully try and get it right," Guthrie said.
"I think the positive signs are that it's hopefully not too serious.
"Fingers crossed, I'd like to play some footy again with him soon."