Collingwood dynamos Jordan De Goey and Bobby Hill will join captain Darcy Moore on the sidelines for the Magpies' top-of-the-table blockbuster with the Brisbane Lions.
De Goey suffered a glute injury during the win over Geelong last week and won't be risked with only two games to go before finals.
Hill left training early on Wednesday with a hamstring issue and will sit out Friday night's match at a sold-out Marvel Stadium.
The Pies are already without superstar Nick Daicos (knee) until around the preliminary final weekend.
"There's a risk-reward attached to this time of year, how much risk you're willing to take on certain things," Collingwood coach Craig McRae said.
"This is not the time we have to take as much risk as maybe potentially in a few weeks.
"We're anticipating that he'd (De Goey) be right (for next week's game against Essendon) but again, it's a risk-reward situation.
"I think if it was a grand final I'd be pushing hard for all to be playing."
In better news for the Magpies, veteran Steele Sidebottom has been declared fit to play after being hampered by an ongoing foot issue that saw him miss against the Cats.
Defender John Noble has also pulled up well after struggling with an ankle issue in the second-half against Geelong.
With some forced changes, Collingwood have opted to hand a debut to defender Jakob Ryan, who was taken in last year's draft at pick 28.
The Pies announced Ryan's debut to the whole playing group out on the ground during training on Wednesday.
McRae confirmed Ryan would start in the 22 and would not be selected as the substitute.
"It's exciting to give someone an opportunity at this time of year," McRae said.
"He gets it through reward and playing above the level in the VFL."
Moore will miss the next two games with a hamstring strain after being subbed out against the Cats.
But the star defender was running at training on Wednesday in a sign he will be right to go for the Magpies' first final.
Collingwood can seal the minor premiership if they defeat the Lions, who go into the game second on the ladder and are two games behind the Pies.
