Magpies captain Scott Pendlebury fears he may have broken his leg as Collingwood lost by 28 points to Port Adelaide at Docklands Stadium.
The 33-year-old was substituted out of the game at quarter-time after landing awkwardly in a first-term tackle.
The six-time All-Australian limped off the ground during the opening term and was immediately assessed by the Magpies' medical staff in the rooms.
And while Pendlebury tried to prove his fitness in a series of run-throughs on the boundary, the 334-game champion was ruled out for the remainder of the match.
Pendlebury said after the game that the injury, which was caused by a knock just above his ankle, felt like a previous setback.
"I've broken my leg before and it's a little bit similar to the pain I experienced with that," Pendlebury told ABC Sport.
"It's really sore around the bone in the middle of my leg, the muscle around that is really tight. I tried to run or kick and it didn't feel right."
Interim Magpies coach Robert Harvey said in his post-match press conference that the club's medical staff wouldn't have adequate information until Pendlebury underwent scans.
"It's a pretty early diagnosis that one," Harvey said.
"All that we know is that he was a bit sore to go back on.
"Until we get further information it's too early for that (call).
"But he was moving around okay just then, so we'll see."
Pendlebury tallied six touches in the first term, two of which were contested.
Collingwood led Port Adelaide by five points at the quarter-time break before sliding to a 14.13 (97) to 10.9 (69) loss.
In a blow to Collingwood's victory chances on top of Pendlebury's injury, the Magpies' medical substitute was 211-centimetre ruck-forward Mason Cox.
There's not a more dissimilar player in the competition to Pendlebury than Cox.
Port Adelaide's win ensured the 300th AFL game of gun midfielder Travis Boak was an occasion to cherish.
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