The night before Laurie Daley was due to announce his team, Mitchell informed the Blues coach he would need to miss game one to recover.
Mitchell was unable to finish South Sydney's loss to the Dolphins at Magic Round, the centre having aggravated the back injury he suffered a fortnight earlier.
It's a crushing blow for NSW, with Mitchell considered a lock to play left centre if fit.
Mitchell will also miss at least next weekend's clash with North Queensland at NRL level but could return after the Rabbitohs' round-13 bye.
Blues captain Yeo was impressed by Mitchell's team-first attitude in stepping aside for Origin I
"I think if you asked (Mitchell), there'd be no one who'd want to play for his state more, particularly with what he's done in that arena," Yeo said.
"I'm obviously disappointed for him, but it's a very selfless act."
Mitchell had a quieter Origin series last year by his lofty standards but has been in superb form since making a full-time shift from fullback to the centres in 2026.
He originally suffered his injury in the Rabbitohs' round-nine loss to Newcastle and was expected to miss a maximum of two weeks.
The 28-year-old returned after just one week, only to leave Friday's loss in the 73rd minute 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.
They took a similar approach with Payne Haas and Brian To'o last year and the pair overcame their injury issues to finish the series as the Blues' best players.
But Mitchell took the decision out of NSW's hands, leaving Kotoni Staggs, Tolu Koula and Casey McLean as selection options at left centre.
Brisbane premiership winner Staggs has missed the past two weeks through suspension but was in fantastic form before that and has played Origin once before.
Koula and McLean are uncapped but have had strong years for Manly and Penrith, respectively.
Canterbury captain 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 best form from his three-time premierships with former club Penrith 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.
Yeo will be joined in camp by at least two Panthers teammates in halfback Nathan Cleary and winger To'o.
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