Penrith might have to plug a few more holes when they face Newcastle next week after a torrid win over the St George Illawarra at Netstrata Jubilee Stadium.
The defending premiers already have State of Origin halfback Nathan Cleary (shoulder) still recovering from off-season surgery.
His fellow NSW teammate Brian To'o (knee) and New Zealand international prop James Fisher-Harris (shoulder) could be joining Cleary in the rehab room.
Fisher-Harris left the game against the Dragons in the 24th minute and didn't return.
"A bit of carnage today. I don't know how bad Fish's shoulder is but it didn't feel like he could go back on," coach Ivan Cleary said.
"Biz has done something to his knee. It's not good but that's the situation we're in."
Cleary said his son Nathan would not be available for the Knights clash in Bathurst but the star halfback is expected to return for the home game against South Sydney at home.
"That's still the plan," Cleary said.
Fullback Dylan Edwards said the latest injury concerns meant a more sombre mood in the Panthers sheds despite back-to-back wins to start 2022.
"Obviously it's not good for those boys and I hope it's not as bad as it seems," he said.
"I don't know time or lengths they might be out, we have to wait until their assessed.
"But we've got some depth in this side so if other guys have to come in they'll do a great job for us."
Lock and skipper Isaah Yeo said the Panthers would once again draw on their wealth of talent in the lower grades.
"The club talks about its development in bringing players through, and I think we've shown that over the last few years ... We trust whoever comes into the team," he said.
Edwards said players were not overly concerned with the new concussion rule that allows independent NRL-appointed doctors in the bunker to remove players, even if a team's medical staff have cleared them to play on.
Both clubs lost a player to an enforced HIA on Friday night - halfback Sean O'Sullivan for the Panthers and then Jack Bird for the Dragons.
"I like the idea of what they're trying to implement but there does seem a few teething problems ... If they could get an independent doctor there at the ground I think that might be better ... It is good they are looking after our wellbeing," Edwards said.
