A typically brutal Origin opener and tight 48-hour turnaround will see top four contenders Newcastle, South Sydney and Canberra keep several interstate stars on ice to start round 13.
Knights big guns Kalyn Ponga and David Klemmer are set to be rested for Friday night's mouthwatering clash with the Rabbitohs, with coach Nathan Brown all but ruling Ponga out of backing up ahead of his return to Newcastle on Thursday.
A final call on Klemmer is yet to be made, but his 51 straight minutes in the middle for NSW had Brown telling reporters he and Ponga "will have to be extremely convincing for me to play them".
Telstra Tracker data revealed Ponga clocked almost 9km at the back for Queensland on Wednesday night - an increase in both intensity and volume on his usual output at club level.
The hamstring injury Ponga suffered last year a week after his Origin debut was firmly in Brown's thinking when it came to his gun No.1 given next Saturday's clash with Melbourne would make for three games in 10 days if Ponga was not rested against Souths.
Match Highlights: Maroons v Blues
The Rabbitohs meanwhile will rest rookie NSW five-eighth Cody Walker, while Damien Cook, Dane Gagai and Cameron Murray are all set to back up.
"Cody Walker won't play but the others will," Rabbitohs coach Wayne Bennett said on Thursday.
"I just don't think it's in his best interests to back up two days later when he hasn't played before at this level. He's got a couple of niggles so it's about making sure he's fit to play next week."
Souths will also be without halfback Adam Reynolds, who has been ruled out indefinitely with a back injury.
Nick Cotric's "issue behind his knee" poses a headache for Canberra coach Ricky Stuart ahead of Friday's stoush with Wests Tigers.
Cotric was unsure of the extent of his injury in the aftermath of Origin, but Stuart said his knee was "stable" after talking to the Blues rookie on Wednesday night.
Blues physio staff said there were no structural issues with Cotric's knee and Stuart said if he was passed fit by team medical staff he would play.
"It was a pretty tense moment, you never like to see guys go down with injuries especially knee injuries," Stuart said on Thursday.
"I don't actually know the extent of it yet but we'll know more today.
"If he gets passed medically he'll obviously be playing, but I'll leave that to the medical boys when we get to Sydney.
"Speaking to him last night he was sore, but I don't think there is any real damage to the knee, coming from the advice of the NSW physio the knee seems to be stable, which is good news."
Stuart expects Jack Wighton and Josh Papali'i to back up from Wednesday night but may lighten Papali'i's usual workload in terms of playing time.
Stuart said he would know a lot more when he meets up with his Origin trio at the team's hotel in Sydney.
Elsewhere Melbourne's Origin quartet of Will Chambers, Felise Kaufusi, Josh Addo-Carr and Cameron Munster are all travelling straight to Auckland ahead of the Storm's clash with the Warriors on Saturday.
The club expects all four to back up at this stage pending assessment over the next 48 hours.