Kalyn Ponga has been ruled out of Newcastle's clash with the Warriors due to his ongoing groin problem and is also out of contention for Queensland's shot at redemption in Origin II.
The star fullback has not played since round nine and the Knights announced on Thursday that he "hasn't been able to achieve the training intensity and volume required to return to play" ahead of his expected return on Saturday.
Newcastle said Ponga would take a week off during the representative round to "continue his rehabilitation process and reassess an achievable return to play timeline", indicating the 23-year-old was not going to be available for the Maroons.
Queensland coach Paul Green is now likely to stick with incumbent fullback Valentine Holmes and sweat on the fitness of Titans fullback AJ Brimson as cover.
Warriors fullback Reece Walsh has also been mentioned as a bolter in the Maroons side.
Queensland were hoping Ponga would be available to bolster their team in the wake of their 50-6 defeat in the series opener in Townsville.
He was named in the Maroons side for Origin I but was quickly ruled out by Queensland's medical staff and returned home less than 48 hours later for further treatment.
Knights coach Adam O'Brien told the media in his post-match press conference a fortnight ago that Ponga's short trip to Maroons camp last month had pushed back the star fullback's return.
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He was hopeful the Knights No.1 would return against the Warriors but indicated he remained under a cloud compared to veteran halfback Mitchell Pearce, who has been cleared to return from his pectoral injury.
The gun fullback's latest setback means Pearce and Ponga are still yet to play together this season, while it was due to be the first time the pair combined with Jake Clifford and Jayden Brailey in the spine.
Newcastle are yet to announce a replacement for Ponga with Connor Watson and Tex Hoy options to play fullback.
The Knights will also be without centre Bradman Best for the next 6-8 weeks due to a syndesmosis injury that requires surgery.
Enari Tuala will slot into Best's spot on the left edge with Kurt Mann on the right side.
Origin II in Brisbane is sold out but tickets are still on sale for game three at Stadium Australia in Sydney on July 14 - get your tickets at NRL.com/tickets.