Melbourne co-captain Jack Viney and key forward Tom McDonald will likely miss the next 6-8 weeks with foot injuries.
Melbourne coach Simon Goodwin told the media on Thursday, saying his star duo are still very sore in the legs.
"They (Viney and McDonald) both had cortisones (injections) during the week. They'll have a couple of weeks off legs so we're not expecting them to be right for six to eight weeks in terms of rebuilding them up," Goodwin said.
"Both those players will be out, but we're trying to set them up as best we can to have impact for when they come in and play for us."
Goodwin also confirmed young forward Bayley Fritsch will make his debut against the Cats, after and impressive JLT performance.
Midfield star Clayton Oliver will take his place in Melbourne's 22, after initial fears he would miss round one with knee soreness.