Penrith have been dealt a double blow, with centre Peta Hiku ruled out for the NRL season and forward James Fisher-Harris sidelined for eight weeks.
Kiwi Test representative Hiku tore both his anterior and medial cruciate ligament in Sunday's loss to Gold Coast, and will undergo surgery in the next fortnight.
Hiku, who scored five tries in 11 games for Penrith after moving across from Manly over the summer, will also miss New Zealand's end-of-season Four Nations campaign, with the injury set to rule him out for at least six months.
Confirmation of Hiku's injury comes on the back of Penrith having already lost fellow starting Kiwi centre Dean Whare for the remainder of the season due to a knee injury.
Waqa Blake is likely to benefit with an NRL recall, while back-rower Isaah Yeo could be forced to make a permanent shift back to the centres.
Yeo moved into the backline last June following a similar injury crisis.
Meanwhile, second-rower Fisher-Harris will undergo surgery on Wednesday on his fractured thumb.
The 20-year-old has played every game of the season after making his NRL debut in round one.