Mitchell Moses has been ruled out the State of Origin opener with Ethan Strange set to make his debut for NSW at five-eighth.
Moses trained with the Blues in Gosford on Monday but complained of soreness in his hamstring at the conclusion of the session.
The Parramatta playmaker was sent for scans with the results ruling him out of game one at Sydney's Accor Stadium on Wednesday.
"It's nothing major but it's too risky 48 hours out from the game," said Blues coach Laurie Daley.
"It's a big loss but Origin you expect nothing different, there's always unexpected things that happen.
"We've got a really good strong group of young men and nothing fazes them."
Canberra five-eighth Strange will partner Nathan Cleary in the halves in his Origin debut.