Blues coach Brad Fittler took time out during his video media conference on Monday to speak to NSW doctor Nathan Gibbs, who advised him that Saifiti would not be right to play next Wednesday.
Broncos prop Payne Haas is likely to be promoted from the bench with Storm veteran Dale Finucane elevated from the reserves list to the interchange.
Mitchell Moses has been called up for his NSW Origin debut and charged with delivering the fourth series whitewash in Blues history, as predicted by NSW's greatest nemesis, Wayne Bennett.
The Parramatta playmaker will have Jack Wighton partnering him in the halves following the absence of injured Penrith stars Nathan Cleary and Jarome Luai.
The Penrith duo's loss is teammate Api Koroisau's gain as well, with the hooker to come onto the bench for his debut as Wighton's utility replacement.
Melbourne rising star Nicho Hynes has been added to the NSW squad for the first time, on the extended reserves bench alongside Storm teammate Dale Finucane.
Moses withstood a late push for South Sydney's Adam Reynolds after producing a strong audition against the Panthers, laying on two tries through kicks despite missing a game-winning shot at goal in a gut wrenching 13-12 loss.
The Rabbitohs halves pairing put on a clinic in South Sydney's dismantling of the Wests Tigers, after which Bennett said he would be plumping for younger halves options that his own club's veterans.
"That's what I'd be doing because while you want to win the third game you've got to keep an eye on what's going forward for next year," the former Maroons coaching mastermind said.
"They've won the series but they won't want to lose the third game, that's part of your instinct.
"But at the same time it's an opportunity to play some players that are younger and have more time with NSW."
Fittler has done exactly that with 26-year-old Moses' Origin call-up coming after a topsy-turvy career that has trended upwards markedly in recent seasons.
Moses was told in 2018 that he was free to leave his Eels contract early after an uninspiring wooden spoon campaign.
Choosing to double down rather than make for the exit, Moses has since led Parramatta to consecutive finals appearances and another strong showing in 2021.
His form has not wavered despite dominating the NRL's contract capers midway through the season, eventually re-signing at the Eels despite a big money bid from Brisbane.
Blues skipper James Tedesco told Fox League on Sunday night that Moses was ready for the intensity of Origin.
"I was stoked, I messaged Mitch earlier today and told him to let me know if he got a call. He let me know this afternoon," he said.
"I was so happy for him, he’s been wanting to get the jersey for a long time and when Nath went down he was a big chance.
"I think he’s got to keep it simple. The role he plays at Parramatta he’s cool and calm especially with his kicking. There’s no pressure on him for this game. He can go out and play some footy if you look at this team.
"He’s got guys like Tommy [Trbojevic] outside him so can give him early ball and he’ll do the rest."
Koroisau can fill a useful utility role, according to Tedesco, as a back-up to starting hooker Damien Cook.
"Api’s been awesome, he’s been in camp the first two games. He can have some versatility in the halves even if his position is at dummy half.
"We can use that to our advantage and find a bit of spark around the middle of the ruck or give Cookie a rest at the back end of the game. They’ve both got that energy around the ruck."
NSW will go into camp for game three on Tuesday, with the Blues to assemble on the Central Coast.
This time last year Hynes still had just one NRL game to his name. Now the 25-year-old's stunning rise, after years of plugging away through NRL and State Cup systems, sees him cap a rich Cronulla deal for next season with Origin honours almost in his grasp.
Elsewhere, Tariq Sims is clear to take his place for the Blues as he was not part of the Dragons players who allegedly broke state COVID-19 protocols and NRL biosecurity orders.
Angus Crichton and Liam Martin keep their back-row spots as well with Jake Trbojevic kept on ice after his pre-Origin II glute tear.
- James Tedesco (c)
- Brian To'o
- Latrell Mitchell
- Tom Trbojevic
- Josh Addo-Carr
- Jack Wighton
- Mitchell Moses
- Daniel Saifiti
- Damien Cook
- Junior Paulo
- Cameron Murray
- Tariq Sims
- Isaah Yeo
- Apisai Koroisau
- Angus Crichton
- Payne Haas
- Liam Martin
- Dale Finucane
- Nicho Hynes