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Penrith are in unfamiliar territory as underdogs for Saturday night's clash against ladder-leading Cronulla.

Penrith's average 16-point winning margin and rarity of back-to-back defeats could spell danger for Cronulla.

Rarely beaten in the last four-and-a-half years, Penrith players were the first to acknowledge last Sunday's's 22-20 loss to Warriors as uncharacteristic and poor.

But they are also adamant it will have no bearing on Saturday night's blockbuster against the top-of-the-table Sharks at PointsBet Stadium.

The Panthers have lost only 18 games since becoming an NRL powerhouse in 2020.

Only twice have they lost again the week after with back-to-back defeats coming during the 2021 State of Origin and during a rare lull early last season.

On the other 15 occasions, Penrith have rebounded with a win and margin of 16.

"I just think because we're pretty honest with each other and pretty honest with ourselves," second-rower Scott Sorensen said.

"We've analysed the game, we've digested it because you've got to get back on the horse as soon as you can.

"We all got together, assessed it, and then the boom box was on again, pumping. The vibes are up again to move on and prepare for this weekend."

Penrith players are, however, well aware there is a perceived chink in their armour this year.

Nathan Cleary is missing for at least the next seven weeks with his hamstring tear, while as many as five other players could be missing to Origin in coming months.

Questions are also being asked about their depth, after yearly raids from rival clubs getting to the point where an all-star team of ex-Panthers looks as dangerous as any on paper.

But Penrith players insist they are unfazed as they push for a fourth straight premiership.

"It's motivating as always," Sorensen told AAP.

"As footy players we always talk about wanting to play the hardest game, you want to play against the best opposition. And that's what's happening.

"Whether people are in or out, it is challenging. I'm not going to say it isn't. But it's also extremely motivating and very exciting at the same time."

Penrith's challenge is highlighted by the fact the TAB have them as outsiders for just the eighth time in three-and-a-half years against Cronulla on Saturday.

But second-rower Liam Martin also insists it's not the first time Penrith have faced questions through their run of dominance.

"Over the few years we've always been challenged, through injuries and through the Origin period," Martin said.

"We've had Nath out for periods of time, and I think we've really stood up.

"We've lost quite a few (players to rivals). But I think the boys that are coming through are going to do a fantastic job.

"They still have that strong belief that we've built here. The culture will hold us in good stead. I don't think anyone's belief has wavered."