The night before Laurie Daley was due to announce his team for game one, South Sydney officials told the Blues that Mitchell would need to miss game one to recover.
It's a crushing blow for NSW, with Mitchell having been in superb form at the Rabbitohs and considered a walk-up start for left centre.
Mitchell originally suffered the injury in the Souths' round nine loss to Newcastle.
He missed a week and returned for the Magic Round defeat to the Dolphins, only to leave late in the second half with his Origin hopes in doubt.
The Blues had been expected to name Mitchell on their team sheet and manage his injury in camp ahead of game one in Sydney on May 27.
But the Rabbitohs took the decision out of their hands, leaving Kotoni Staggs, Tolu Koula and Casey McLean as selection options.
Stephen Crichton has already been told he will retain his right centre spot despite questions over his form and shoulder injury.
Out of sorts since returning early from a serious AC joint injury, Crichton showed glimpses of his three-time premiership winning best in Canterbury's loss at Magic Round.
Crichton has appeared tentative in his defence and passing since returning in round seven, but has not missed a Blues games since his debut in 2022.
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