Colin Sylvia (jaw) and Austin Wonaeamirri (leg) were the latest Demons to be added to the injury list, after being hurt during Melbourne's loss to West Coast in the NAB Challenge series on the weekend.
Football operations manager Chris Connolly said that while the injuries were frustrating, the club was remaining philosophical about its position.
"They're significant players for us, but that's footy," he said.
"We know they'll all resume with the team when the season unfolds and we look forward to that and it creates opportunities for others."
Sylvia and Wonaeamirri join Paul Johnson (foot), Cale Morton (knee), Liam Jurrah (shoulder) and Daniel Bell (shoulder) as other first-choice players who will miss the season opener.
Meanwhile, 2008 NAB AFL No.1 Draft pick Jack Watts is a chance to line-up for Casey this weekend after battling a back injury this pre-season.
Connolly said a number of Melbourne players will play for Casey this weekend.
"We're just finalising that group and Jack might be part of that group," he said.
"He might have a run this week."