The Cronulla Sharks are facing a backline injury crisis ahead of Saturday's preliminary final against the Penrith Panthers, with Jesse Ramien and Kayal Iro both set to be ruled out.

The duo, who are the Sharks' centres, have been a critical part of the Sharks' run to the top four this season.

Cronulla have used a style of game which has a chance of running with the Panthers this weekend, built off their back five running the ball hard.

All five - Iro, Ramien, wingers Ronaldo Mulitalo and Sione Katoa, and fullback William Kennedy, have averaged well north of 100 metres per contest over the course of the campaign.

Metres from the back have been the catalyst for Penrith's run to three straight premierships, with the club pushing for a fourth, and a fifth straight grand final when they clash with the men from the Shire at Homebush on Saturday evening.

But now Cronulla will be missing two cogs in their wheel to go with Penrith, according to The Sydney Morning Herald who are reporting both are doubtful to play.

Ramien already missed the first week of the finals for the Sharks on the back of a syndesmosis injury picked up during the final round of the season.

He returned last week, but was unable to complete the game as Craig Fitzgibbon's side managed to see off the North Queensland Cowboys, and it's believed he is all but certain to be ruled out.

Iro, on the other hand, is racing the clock to be named fit, with the centre suffering a biceps injury during the game against the Townsville-based side.

It's understood he is a chance to play, but that Mawene Hiroti has been withdrawn from the Newtown Jets' grand final against the North Sydney Bears to provide cover.

He will only play for the Sharks if both centres are out, with Siosifa Talakai the first man to be brought into the side, while breakout utility Daniel Atkinson will play from the bench for the Sharks as the first man into the side. He too has been withdrawn from Newtown's grand final preparations.

Cronulla will update their team list 24 hours before Saturday night's kick-off, with a clearer picture of Iro and Ramien's fitness expected at that time.