North Melbourne were forced into making their tactical sub change in the opening quarter of Sunday's game after defender Griffin Logue sustained a knee injury just minutes into the Roos' clash with Geelong at Kardinia Park.
An attempted tackle on Cat Mitch Duncan left Logue in the hands of club trainers and he slowly made his way to the interchange before requiring further assessment.
"Griffin's got a serious knee injury, but we're not certain what it is yet," coach Brett Ratten said after the loss.
"He'll go for scans and we'll have more then, but he's going to miss some footy."
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The Roos then lost star midfielder and co-captain Jy Simpkin for the second half after the onballer sustained a concussion prior to the main break.