Penrith are facing absences greater than most clubs experience during the State of Origin period, with Nathan Cleary headlining a list of four representative stars ruled out against Newcastle.
The Panthers confirmed on Thursday that Cleary would miss Saturday's top-of-the-table NRL clash, after pushing back his return from shoulder injury another week.
Also James Fisher-Harris has failed to recover from a minor shoulder injury suffered in last week's loss to St George Illawarra, while Liam Martin has succumbed to a leg injury incurred at training.
The trio join NSW star Brian To'o (knee) and front-rower Moses Leota (shoulder, to more months) on the sideline.
In total, it means the defending premiers will be without nine players from last year's grand final team on Saturday, with Matt Burton, Paul Momirovski, Kurt Capewell and Tyrone May having all left the club.
The injury woes leave Jarome Luai and Apisai Koroisau as the only remaining representative players in the Panthers side, with Sean O'Sullivan to remain at halfback and Spencer Leniu likely to partner Matt Eisenhuth in the front row.
"They're obviously big losses but it just turns into another game of footy," Koroisau said.
"You're going to have injuries through the year no matter where you are playing or what team you're in.
"You just have to adapt as best you can. We have so much faith in all the guys who have been waiting for the opportunity."
Penrith players are hopeful that Cleary will be able to return next week against South Sydney.
The Panthers initially stated he would return in that game, but his appearance on an extended bench this week came with some hope he would return early.
He was never considered more than an outside chance, but teammates believe he is close to full fitness.
"He's been awesome," Luai said.
"He's full contact and stuff like that. We're not taking it easy on him on the training paddock. Hopefully we see him next week."
It comes as Newcastle hold onto hope rep stars Kalyn Ponga and Daniel Saifiti will return for the crunch clash after losing David Klemmer and Lachlan Fitzgibbon to knee injuries.
