The Canberra young gun suffered the injury at the Blues' first field session of their camp for game three, held at Gold Coast's Cbus Super Stadium on Thursday.
NSW remain hopeful bench playmaker Strange could shake off the injury in time to be fit for Wednesday's match against Queensland in Brisbane.
But staff will monitor the situation and are ready to request NRL permission to draft in a player from outside their 20-man squad.
Isaiya Katoa would have been the likeliest option, after being on stand-by when a hamstring injury troubled Mitchell Moses ahead of Origin II, but the Dolphins halfback suffered an arm injury in last week's defeat of the Warriors that will preclude him from selection.
Strange's ankle issue continues a horror run of injury scares for the Blues this series.
Moses was formally ruled out of the series opener the day before the game, before Casey McLean went down with a quad injury in camp for Origin II.
Strange was revelatory on Origin debut in the series opener, helping NSW seal a 22-20 win, before being restricted to a cameo from the bench in the game-two loss.
In better news, Stephen Crichton entered camp for the decider feeling the best he has since suffering his long-standing shoulder injury.
On Thursday, he described his call to sit out Origin II as "the hardest decision I had to make".
Usually a walk-up starter for the Blues, Crichton was named in the squad for the eventual 44-24 MCG thrashing, only to withdraw that same evening.
The 25-year-old had been troubled by an AC joint injury since Canterbury's loss to South Sydney on Good Friday, frequently requiring painkilling injections.
Crichton had lined up in the Blues' game-one victory, but still below his best ahead of game two and feared he would have been a "liability" had he remained in camp.
"It was the hardest decision that I had to make," Crichton said.
"Just knowing that I couldn't train and couldn't get the repetition in with the boys and build that connection, I didn't want to be a liability.
"I knew, going back to Dogs, I could get that rest at the start of the week and do what I had to do."
Crichton has managed to remain afield with the improving Bulldogs in recent weeks, negotiating a surprise switch to five-eighth in that time.
He tested his shoulder out during the Blues' wrestling session at their Kingscliff camp on Wednesday and pulled up well from heavy contact with the other outside backs.
"This is probably the best I've felt as well, coming into camp," said Crichton.
He will need all the strength he can muster in the decider, lining up against Queensland's left edge, where strike weapons Kalyn Ponga, Hamiso Tabuai-Fidow and Cameron Munster do their best attacking work.
"It's going to be a massive task for our right edge, but I'm very excited to walk towards the challenge," Crichton said.
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