Blues halfback Nathan Cleary is set to miss the State of Origin decider on July 10 with a suspected syndesmosis injury.
NSW medical staff have indicated that Cleary won't recover in time to help NSW on their quest for consecutive series wins over Queensland.
Cleary failed to return for the second half of the Blues' 38-6 game two victory after succumbing to a right ankle problem at Optus Stadium.
The 21-year-old sustained the damage midway through the first stanza, grimacing in pain as he received attention from the team trainer.
He continued on but handed the goalkicking duties to five-eighth James Maloney after NSW's third try due to the issue.
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Cooling down at half-time proved problematic for the playmaker and he went to the bench when the final 40 minutes began with his foot wrapped in ice.
Bench forward Wade Graham was shifted into the halves alongside Maloney in the second half.
Mitchell Pearce, who was ruled out of Origin II with a minor hip injury, is the frontrunner to partner Maloney in a few weeks' time.