Penrith have ruled superstar halfback Nathan Cleary out of the first three weeks of the NRL season following off-season shoulder surgery.

Cleary steered the Panthers to a premiership last year while nursing the injury he picked up playing for NSW in State of Origin.

There had been speculation Cleary would play in Penrith's season opener against Manly on Thursday, but on Tuesday the club confirmed he would miss their opening three games against the Sea Eagles, St George Illawarra and Newcastle.

"With a long and challenging season ahead of us, it's critical that we give Nathan the time he needs to return at his physical best," coach Ivan Cleary said.

"While it's obviously a difficult decision and of course we would have loved to have him out there, we believe this will ensure Nathan has the best opportunity to play throughout the year at the level he demands of himself."

Sean O'Sullivan is expected to partner Jarome Luai in the halves after signing from the Warriors. The Panthers play South Sydney in round four.

AAP