Melbourne have paid a huge price for Sunday's AFL win over Greater Western Sydney, losing star recruit Mitch Clark for the rest of the year.
The former Brisbane forward has sustained a foot fracture known as a Lisfranc tear, scans on Monday showed.
"This is incredibly unfortunate for Mitch and for everyone involved with the club," Demons football manager Josh Mahoney said.
"His leadership and influence on the group - on and off the field - has been outstanding since arriving at the club.
"The club will now investigate the best course of action to repair and rehabilitate Mitch's injury.
"We want to ensure he has a smooth return to football in 2013."
Clark had made a superb start to his Demons career, kicking 29 goals in 11 games to comfortably lead Melbourne's scoring.
The one small ray of light was that regular defenders Jared Rivers and Colin Garland had shown good form in attack, with seven goals between them against the Giants.
"We are building flexibility into our players and now have several options," Mahoney said.
Carlton defender Jeremy Laidler is also unlikely to play again this season after being booked in for knee surgery.
Laidler dislocated his kneecap for the third time in five months while making his latest comeback through the VFL on Saturday.
Hawthorn captain Luke Hodge and Collingwood midfield star Scott Pendlebury have both ruled themselves out of making AFL returns this weekend.
Hodge, who has played just two games this year due to calf and knee injuries, said he needed to build fitness and would not face Carlton at the MCG on Friday night.
"I need a few more weeks or sessions of just running and kicking, just so when I do get into the intensity of a game that a hammy or a quad or something has had enough work," Hodge told Melbourne's SEN radio.
Pendlebury, who has missed two games with a cracked tibia in his right leg, will not play against Fremantle at the MCG on Saturday.
"Hopefully I can be back for that Carlton game," he said of the clash with the Blues six days later.
Adelaide hope star forward Kurt Tippett can play against Richmond at AAMI Stadium on Saturday despite being subbed off with concussion against North Melbourne on Sunday.
Tippett is likely to be named in Adelaide's squad on Thursday night ahead of a Friday fitness test.
Port Adelaide will be without skipper Dom Cassisi for Sunday's Skilled Stadium clash with Geelong because of a hip injury.
And Essendon small forward Angus Monfries will miss at least the Bombers' next two games, after scans showed he tore a hamstring during Saturday night's win over Fremantle.