Nathan Cleary has been sidelined with a minor hamstring injury, Penrith have confirmed to AAP.
The superstar halfback was substituted out in the final 10 minutes of the Panthers' 34-12 win over Brisbane on Thursday night.
After feeling more discomfort than anticipated, the 26-year-old was sent for scans.
The Panthers are expected to release a formal update on Cleary's condition on Tuesday.
He will not be named in the team to face the Sydney Roosters on Thursday and could also miss the visit to Manly on April 6.
The Panthers have a bye in round six and are hopeful Cleary could return for their first game after that - against Wests Tigers in Bathurst on April 20.
Former Canberra playmaker Brad Schneider is expected to make his club debut in Cleary's place, lining up next to Jarome Luai in the halves at Allianz Stadium this week.
Cleary needed six weeks to recover after tearing his left hamstring in a tight win over St George Illawarra last June, missing the final two games of NSW's State of Origin campaign.
Penrith also have doubts over James Fisher-Harris, whose shoulder injury they describe as a week-by-week proposition.
The damage is not thought to be severe but the prop missed last week's win over the Broncos and is no certainty to return to face the Roosters.
A low-grade hamstring strain is likely to keep Roosters prop Lindsay Collins out of Thursday's clash.
Collins has commenced rehabilitation, the Roosters said on Monday, with back-up five-eighth Sandon Smith (elbow) also in doubt.
The Roosters said Smith suffered a "significant medial ligament injury to his left elbow" just before halftime of Friday's 48-6 hammering of South Sydney.
In better news for the Roosters, halfback Sam Walker has been cleared of concussion and will line up against the Panthers.
The bunker's independent doctor originally ruled Walker had suffered a category-one head injury in the second half of Friday's game, which would have ruled him out for 11 days.
But the NRL's chief medical officer has since engaged two other independent doctors to assess Walker, whose injury was downgraded to category two.