The depleted Sydney Roosters have produced an early contender for upset of the NRL season, stunning four-time reigning premiers Penrith in a pulsating 38-32 win.

To make matters worse for the Panthers, star fullback Dylan Edwards left the field midway through Friday night's second half with an apparent groin injury.

The Roosters were $11 outsiders ahead of Penrith's first clash at their adoptive home CommBank Stadium.

They were missing 788 games of first-grade experience through injury or suspension - after losing more than 1,000 more in the off-season - and had not beaten the Panthers in their past 10 meetings.

But what was supposed to be a procession for the NRL's champions was instead a tit-for-tat battle with a Roosters side who proved their season may not yet be a lost cause.

After last week's hammering from Brisbane, the Roosters had looked the better side in a tight contest and finally broke free with tries in back-to-back sets midway through the second half.

Superb in only his third game, rugby convert Mark Nawaqanitawase threw the last pass for Daniel Tupou to score, before a break down the left put Sandon Smith in.

NSW fullback Edwards went off after the second of those tries, apparently injuring his groin in pursuit of Smith as the Roosters took a 10-point lead.

Given he played the 2021 grand final on a broken foot, any injury that forced Edwards from the field will be cause for concern.

Down 38-26 after taking a penalty goal with seven minutes remaining, the Panthers looked ready for a fast finish, spreading left to put Casey McLean in.

A second penalty goal made it a one-score game while Roosters forward Salesi Foketi was in the sin bin for a high shot.

But on the last play of the game, Tupou tackled prolific finisher Brian To'o into touch as he attempted to ground the ball for an equalising try.

Penrith had managed to overcome a shaky start to beat Cronulla in round one but never found their rhythm after their left centre Paul Alamoti swanned over for the opener inside three minutes.

The Roosters' three first-half tries all came after the Panthers' back three dropped Chad Townsend kicks, with McLean responsible for two of those knock-ons.

Penrith struggled to contain the energetic Roosters' second-phase play and missed an uncharacteristic 43 tackles.

The 38 points they conceded were the most they have bled in any game that Nathan Cleary has played since 2018.

Next week's grand final rematch with Melbourne is set to provide a major litmus test for a Panthers side still clearly adjusting to life without Jarome Luai and James Fisher-Harris.