Payne exited with a ruptured patella tendon in his left knee in the Lions' 17.5 (107) to 13.18 (96) home defeat to GWS on Saturday.
The result dropped Chris Fagan's side to third sport on the ladder, with  just two wins from their past six games.
Payne and Lincoln McCarthy have both been ruled out for the rest of 2025 with knee injuries, while star playmaker Keidean Coleman (quad) will miss another month.
Eric Hipwood was sent back to cover Payne against the Giants, while Darcy Gardiner looms as the likely replacement in a huge test against second-placed Geelong at GMHBA Stadium on Friday night.
Gardiner was pulled out of Brisbane's reserves team for their VFL game on Sunday, with an eye to playing against the Cats five days later.
Tom Doedee, who did play in the VFL game, is another option for the Lions but is yet to feature at senior level since his move from Adelaide at the end of 2023.
Retired Essendon champion Matthew Lloyd isn't convinced those options will be enough for the Lions to repeat their September success.
"I don't think they (can) cover him," Lloyd, now a prominent media figure, said on Nine.
"Gardiner's an OK player, but he's been playing as a forward and probably lacks the mobility and the speed of what Payne does."
Brisbane overcame a raft of season-ending knee injuries last year - including Coleman, McCarthy, Gardiner and Doedee - before destroying Sydney in the grand final.
Lloyd doubts their ability to do it again.
"I ruled it out last year, but now they've lost the bookends," he said.
"(Premiership forward Joe) Daniher I know hasn't been there - he's retired - but losing Payne and Daniher makes it pretty hard."
High-flying Geelong (10-4) are on a five-match winning streak after thumping Essendon by 95 points on Saturday.
The Cats have also beaten the Lions across Brisbane's past 13 visits to Kardinia Park.
A key focus will be accuracy in front of goal, with coach Chris Fagan conceding the Lions blew another golden opportunity against GWS.
"We'll just keep working away on that and not become too psycho about it because everyone will talk about it," Fagan said post-match on Saturday.
In a club statement on Sunday, Brisbane said the 25-year-old Payne will undergo surgery as soon as possible.
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