Uncapped Dolphins centre Jack Bostock replaces Nawaqanitawase on the bench as the Blues fight to clinch the three-match series with a win on Wednesday night.
McLean strained his right quadriceps muscle in the warm-up at Central Coast Stadium on Saturday as the Blues held their last field session before flying to Melbourne.
After debuting in the game-one win, the Penrith centre had been on track to overcome a minor ankle issue and replace the injured Stephen Crichton for his first Origin start.
Instead, McLean hands left-centre duties to Manly's Tolu Koula, who shifts in from the wing.
That clears the way for code-hopping Sydney Roosters winger Nawaqanitawase to come into the starting side as part of a backline shake-up.
"We've trained that way for three sessions, Wednesday, Thursday and also today," said Blues football manager Frank Ponissi.
"So, if (the injury) was going to happen, it's the best possible way for it to happen."
In-form Dolphins centre Bostock joins the six-man bench after the NRL granted NSW permission to draft in a replacement player from outside their initial 20-man squad.
Like Bostock is now, Nawaqanitawase had initially been considered unlikely to get game time unless there had been an injury.
But a whirlwind Origin debut is the latest twist in the remarkable tale of Nawaqanitawase, who will return to rugby union next year.
Still only 25, Nawaqanitawase has played at an Olympics, won caps for the Wallabies and featured for the Kangaroos in last year's Ashes whitewash.
He has played just 36 top-flight games of rugby league since his NRL debut with the Roosters, yet still carved out a reputation as one of the code's most skilful players.
"The whole experience that I've had leading up to this point, it's been amazing," Nawaqanitawase told AAP prior to Saturday's shock elevation.
The Origin debut is further vindication of Nawaqanitawase's decision to switch codes in mid-2024.
"I know I haven't done anything yet for this team (NSW), but what I've done for the Roosters and Kangaroos and the whole journey has been amazing," he said.
"I took a massive gamble, but I've really felt the rewards."
McLean is expected to spend the next seven to 10 days on the sidelines, and has been tipped for future Origin action by Blues hierarchy.
"He's worked so hard the last few days to get his ankle right and he was feeling fantastic going into the session. For this (injury) to happen is really disappointing," Ponissi said.
"But, like Laurie (Daley, coach), I have no doubt that Casey will be back."
McLean's quadriceps strain is the second mid-camp injury suffered by a Blues player this year after Mitch Moses hurt his hamstring ahead of Origin I.
The five-eighth returned to training with his teammates on Saturday and is expected to be fit in time to line up at the MCG.
Moses was still wearing a compression sleeve on Saturday, but stretched and ran with ease after being restricted in his training loads earlier in the week.
"Mitch is good," Ponissi said on Saturday.
"He and all the rest of the team got through OK. We're really happy about that."
9°C