Melbourne expect star midfielder Clayton Oliver to be unavailable for the "short term" and Western Bulldogs defender Jason Johannisen will miss at least two months with a severe hamstring injury.
Brownlow Medal fancy Oliver strained a hamstring in the Demons' four-point defeat to Port Adelaide last Friday night.
He played out the game but is unlikely to recover in time to face Fremantle on Saturday.
Melbourne have a big few weeks ahead as they take on the Dockers, Carlton and flag favourites Collingwood at the MCG before their mid-season bye, then reigning premiers Geelong at their GMHBA Stadium fortress.
"Clayton had some soreness at the end of the game and following a clinical assessment from the physios and the medical team, scans have shown that he's got a hamstring strain," Demons high performance boss Selwyn Griffith said.
"At this early stage, we anticipate Clayton won't be available in the short term.
"His return to play will ultimately be guided by his ability to deal with increased loads and reconditioning.
"As such, we will have greater clarity as Clayton progresses through his program."
Oliver is fifth in the AFL coaches' association voting and is a proven Brownlow poller, finishing equal-fourth last year, third in 2021 and equal-10th in 2020.
The gun midfielder has missed only one game through injury in the past six seasons.
The 2021 premiership player is one of Melbourne's biggest stars, winning their best-and-fairest award four times, as well as three All-Australian selections.
Bulldogs speedster Johannisen suffered a high-grade tear in his left hamstring during his side's 45-point win against Adelaide in Ballarat on Saturday.
Scans have revealed the extent of the 30-year-old's injury, with the Bulldogs predicting at least eight weeks on the sidelines.
"Being an over-stretching injury whilst at speed, our clinical suspicions of a high-grade injury were confirmed with the MRI that showed extensive damage," Bulldogs head of sports medicine Chris Bell said.
"JJ is the ultimate professional and will get to work with our rehab team to get back playing this home and away season but we anticipate that he will miss eight to 10 games."
