The Rabbitohs travel north to face a Cowboys side that welcome back two of their best in Jason Taumalolo and Lachlan Coote on Friday night.
The Broncos face their first trip to ANZ Stadium in 2017, travelling to face the Canterbury Bulldogs in a match-up with big implications for both sides.
Two of the best performers from Round 4 renew hostilities in Sydney's battle of the beaches.
Outstanding performances from Paul Vaughan and Josh Dugan have guided St George Illawarra to a comfortable victory over the Warriors.
Melbourne have stormed back from an early 14-point deficit to extend their unbeaten start to the year with a gutsy win over the Wests Tigers.
Rampaging back-rower Coen Hess has shrugged aside the absence of Jason Taumalolo and Matt Scott to seal the Cowboys' 32-26 win over the Titans on Saturday.
James Segeyaro returned to the NRL as the Cronulla Sharks ground their way to a 20-6 win over an error-prone Parramatta Eels side at ANZ Stadium on Saturday.
A red-hot Manly side exploded out of the blocks to hand the Bulldogs a 36-0 defeat at Lottoland on Saturday afternoon.
A field goal from Broncos winger Jordan Kahu has proved the difference as Brisbane edged Canberra by one point at Suncorp Stadium on Friday night.
The Panthers have hit form, running in seven unanswered tries in a comprehensive victory over the Knights at Pepper Stadium on Friday night.