Jack Wighton will play five-eighth for NSW in State of Origin III after Jarome Luai was ruled out of the series finale with a knee injury.
Luai was hurt in Penrith's 13-12 win over Parramatta on Friday night when his foot was caught in a second-half tackle, and while he required attention on field, managed to play on.
However the 24-year-old was taken for scans on Saturday morning before they revealed some minor damage.
The Blues five-eighth was told he would be in a knee brace for at least a week, before NSW officials decided he would not be brought into camp.
It comes as another significant blow to the Blues' hopes of a whitewash, after they already lost Luai's halves partner Nathan Cleary with a shoulder injury.
The Penrith half had earlier tried to downplay the issue, laughing it off as a cork immediately after the game.
"I was thinking about Nathan a bit out there, more courageous thoughts," Luai said.
"He played through a lot worse injury than I did so I thought I could do a job for my team here and stick solid.
"It was a bit uncomfortable in certain positions but I just wanted to do a good job for my team and stay out there and help them with my leadership.
"I tried to do a few kicks and it was a bit sore but it feels good."
The blow also represents a dent to Penrith's premiership tilt, given they now face some time without both of their starting halves.
They have the bye next week, but Cleary is already out for at least a month and they've lost both games played without the duo this year.
Luai's injury opens up Fittler's squad and causes headaches for selectors before its announcement on Sunday.
Blues advisor Greg Alexander revealed on Fox League on Saturday night that Wighton would play at No.6, handing him a first start in the halves at Origin level.
That leaves NSW searching for a new utility, with Api Koroisau, Clint Gutherson and Matt Burton the options for the No.14 jersey.
The halfback position also is now a battle of two, with the experience of Adam Reynolds an option against the potential of Mitch Moses.
The other decisions for selectors centre around whether Jake Trbojevic is fit to return from a glute injury and how they create room for him in the pack.
Angus Crichton was a straight swap for him in Game II, but would be expected to hold his spot.
Meanwhile, there are also suggestions the NRL could face a battle to get Melbourne players into and out of camp due to border restrictions, with the league still weighing up where to play the game.
NSW confirmed on Saturday they would train out of the Central Coast while in the NRL bubble, which forms part of Victoria's red zone.