Penrith five-eighth Jarome Luai is aiming to return from his MCL injury by the last week of the regular season at the latest.
The Panthers told AAP Luai would be sidelined for up to six weeks but coach Ivan Cleary is hoping he will have the chance to take the field before the finals series begins in the second week of September.
Penrith face fellow premiership hopefuls North Queensland in the last round of the season in a match-up that could recur in the finals.
Sean O'Sullivan will line up in the meantime at five-eighth, marking the first time since 2019 Nathan Cleary has had a halves partner other than Luai.
"He's currently in a knee brace while the ligament heals," Panthers physio Pete Green said of Luai.
"He will then move through a process of reclaiming range of movement, static, then some dynamic strength and finally into rehab running and a modified team training phase."
Luai's is the first significant injury suffered by a member of Penrith's best 17 since winger Brian To'o and Moses Leota returned from knee and shoulder injuries, respectively, in early May.
Leota suffered a thumb injury in Penrith's round-18 win over the Wests Tigers but could line up against derby rivals Parramatta on Friday night.
The Panthers will name the premiership-winning prop in their 19-man squad on Thursday night and rate him a good chance of recovering in time to play.
Back-up hooker Mitch Kenny will miss the Eels game with an injury suffered against Cronulla but could be back to face Canberra next weekend.
Stephen Crichton, who went in for plastic surgery after the win over the Sharks, is also a chance to return for round 21.
Crichton's ear was damaged in a tackle from Dale Finucane that also left the Panthers centre concussed. He spent most of this week at home resting.
