Melbourne's Aaron vandenBerg and Joel Smith will both miss the club's opening round clash against Port Adelaide on Saturday.
An aggravation of a previous ankle issue could keep vandenBerg on the sidelines for up to a month, whilst Smith could miss up to six weeks with a groin injury.
Smith played through the club's final JLT Community Series match against Brisbane with the injury, to assist with rotations.
Suggestions that the club's medical staff mishandled the injury were rejected by coach Simon Goodwin.
"Joel had acute awareness of his groin. It certainly wasn't going to change the outcome (of the diagnosis) so in the end we just need to get it settled for a couple of weeks and then re-load him," Goodwin said in a press conference.
"We certainly respect groin injuries and the load around that so that's what we're going to do as a club."
Scans were taken on vandenBerg's ankle, however the exact time frame of the injury is unknown.
"(The ankle) is likely to need a couple of weeks of unloading," Melbourne's elite performance manager Dave Misson told the club website.
"We don't think it's too serious at this stage, but if you unload it for a couple of weeks you then need a couple of weeks to re-load it, but we'll find out a bit more later in the week."
Previous complications with vandenBerg's ankle kept him out of football for 18 months, which has led the club to advise him to take a cautious approach.
He's had some significant surgical intervention there in that ankle and it's something he's going to have to manage for the rest of his career, I'd say," Misson said.
The Demons play Port Adelaide on Saturday at the MCG.