It will be the second game of an Optus Stadium double-header with the Dolphins and Knights doing battle prior. Cronulla are coming off a disheartening 28-0 loss to defending premiers Penrith at BlueBet Stadium.
South Sydney, meanwhile, pulled off an ugly 32-18 win against the Wests Tigers in Tamworth.
The Sharks will be without fullback Will Kennedy after the fullback picked up a hamstring strain against the Panthers that will keep him sidelined for six-to-eight weeks whilst Oregon Kaufusi is out with a fractured finger.
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They join Dale Finucane and Teig Wilton in the casualty ward after both forwards were ruled out with season-ending injuries.
Connor Tracey shifts to the back to cover the absence of Kennedy with Ronaldo Mulitalo returning onto the wing after missing their Round 22 outing with a jaw issue.
Jesse Colquhoun returns onto the interchange in place of the injured Kaufusi.
Hame Sele is out through injury for the Rabbitohs with Thomas Burgess starting up front and Tallis Duncan coming onto the interchange whilst Michael Chee Kam replaces Jacob Host in the second row.
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The two sides last met in Round 1 this year with South Sydney coming away with a 27-18 win at PointsBet Stadium behind a Campbell Graham double.
The Rabbitohs have beaten the Sharks in four of their past five but have lost their past three games in Perth.
Having won just three of their past eight, Cronulla are in need of a rapid change of fortunes as the finals race begins heating up.
Currently sitting seventh, the Sharks are one of six teams in between 24 and 26 competition points and have clashes against the Titans, Cowboys, Knights and Raiders to look forward to after this one.
Souths, meanwhile, are currently sixth having won just three of their past nine and still have meetings with the Dragons, Knights, and Roosters to prepare for along with a Round 26 bye.
The Rabbitohs enter this one as short-priced favourites with bookmakers forecasting Cronulla’s recent woes to linger as their injury list continues to mount.
Kick-off: Saturday 5 August (7:35pm), Optus Stadium
Sharks squad: 1. Tracey; 2. Katoa; 3. Ramien; 4. Talakai; 5. Mulitalo; 6. Trindall; 7. Hynes; 8. Hamlin-Uele; 9. Brailey; 10. Rudolf; 11. Nikora; 12. Graham (c); 13. McInnes; 14. Williams; 15. Hazelton; 16. Hunt; 17. Colquhoun; 18. Moylan; 19. Iro; 20. Hiroti; 21. Hau Tapuha; 22. Atkinson
Rabbitohs squad: 1. L Mitchell; 2. Johnston; 3. Tass; 4. Graham; 5. Milne; 6. Walker; 7. Ilias; 8. Arrow; 9. Cook; 10. Burgess; 11. Koloamatangi; 12. Chee Kam; 13. Murray (c); 14. Moale; 15. Havili; 16. Cartwright; 17. Duncan; 18. Munro; 19. Host; 20. S Mitchell; 21. Mamouzelos; 22. Hawkins
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