Carlton have confirmed that defender Sam Rowe suffered a serious knee injury in his side's 35-point AFL loss to Fremantle in Perth.
Rowe injured his knee early in the match, but was given the green light to return to the field late in the first term.
His return was short-lived, with Rowe's knee buckling when he leaned against his opponent as the ball came towards them.
Scans on Monday confirmed he has ruptured the anterior cruciate ligament in his right knee.
While the Blues said Rowe will consult with specialists, one option is a season-ending reconstruction.
"Sam is a strong character who has been through considerable adversity before and bounced back," said Blues football boss Andrew McKay.
After Sunday's loss, Blues coach Brendon Bolton defended the decision of his club's medical staff to allow Rowe back onto the field.
"No, true professionals our doctors, true professionals," Bolton said.
"I'm just crossing my fingers it's all OK."
Forward-turned-defender Liam Jones now looms as the frontrunner to replace Rowe.
Jones has played predominantly as a forward during his 83-game career with the Bulldogs and Blues.
But the 26-year-old has been successfully used in defence in the VFL this season.
Carlton could also be without Dale Thomas for Sunday's clash with North Melbourne at Etihad Stadium.
Thomas copped a hip to the head from teammate Alex Silvagni during the second quarter of Sunday's loss to Fremantle.
The former Magpie had blurred vision after the incident, and was ruled out with concussion for the rest of the match.
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