Halfback Daly Cherry-Evans was favourite to captain Queensland in the State of Origin series but may not be fit for the opener.
Brisbane Broncos claimed only their second win of the season, while Wests Tigers came from 14 points down to beat Gold Coast Titans.
Melbourne Storm are seeking a seventh straight win over New Zealand Warriors as round seven of the 2019 NRL season kicks off on ANZAC Day.
James Maloney appeared to have set Penrith Panthers on course for a big away win until Cronulla Sharks recovered spectacularly.
Melbourne Storm will look to extend their unbeaten start to six games on Friday when they host defending champions Sydney Roosters.
A four-try haul from Cody Walker helped South Sydney Rabbitohs to victory, but Newcastle Knights' slump continued.
Cameron Smith is just two points shy of becoming the joint-highest points scorer in NRL history ahead of the Storm's clash with the Cowboys.
South Sydney Rabbitohs were beaten for the first time in 2019 and coach Wayne Bennett was unimpressed with their attitude against Manly.
We give you the best Opta facts on round four of the NRL season, which begins with 2018 champions Sydney Roosters hosting Brisbane Broncos.
Cronulla blew the Cowboys away on Paul Gallen's big night, while Melbourne Storm made it three NRL wins out of three.