The Panthers have confirmed star trio Nathan Cleary, James Fisher-Harris and Liam Martin will miss Saturday's clash with Newcastle.

Cleary (shoulder), Fisher-Harris (shoulder) and Martin (leg) won't feature in Ivan Cleary's selection planning for Round 3 in what will be a major blow for the reigning premiers.

Penrith have named J'maine Hopgood, Chris Smith, Robert Jennings, Lindsay Smith, Soni Luke and Kurt Falls as part of his seven-man reserves cohort, with Nathan Cleary having already been named among the septet.

The Panthers will come up against a fellow undefeated side in Newcastle in what is an early-season first vs second encounter.

The Knights are currently perched atop the NRL ladder after the opening two rounds, having defeated the Roosters and Tigers in dominant fashion.

NRL Rd 23 - Panthers v Rabbitohs
BRISBANE, AUSTRALIA - AUGUST 20: Nathan Cleary of the Panthers is tackled by Cameron Murray of the Rabbitohs during the round 23 NRL match between the Penrith Panthers and the South Sydney Rabbitohs at Suncorp Stadium, on August 20, 2021, in Brisbane, Australia. (Photo by Chris Hyde/Getty Images)

Their chances of extending an impressive start to their 2022 campaign are sure to be buoyed by the absences of the aforementioned trio, while star flyer Brian To'o is also set to miss through injury.

Cleary, Martin and Fisher-Harris are tipped to be in contention for the Panthers' Round 4 clash with South Sydney in what will be a grand final rematch on Friday, April 1.

Penrith will confirm their 19-man squad to face the Knights at Carrington Park on Friday afternoon at 3pm.