The Rabbitohs confirmed on Saturday that skipper Murray suffered a hip flexor injury in Thursday night's NRL mloss to Penrith, ruling him out for between six and eight weeks.
Murray's injury means he is no chance of playing for NSW in the series opener on June 5, and would be unlikely to be fit for Game II on June 26.
The backrower has been a regular in Origin for the Blues since his 2019 debut, missing only two games through injury since then, in 2020.
But he has appeared battered and bruised through Souths' nightmare start to 2024, with the last-placed Rabbitohs struggling for form across the park.
The Rabbitohs' injury situation is now so dire that former North Queensland forward Gehamat Shibasaki has answered an SOS call to join the squad from Souths' Queensland Cup affiliate Townsville Blackhawks.
Shibasaki, who arrives in Sydney this weekend, will join the Rabbitohs on a week-by-week basis and is available for selection in next weekend's clash against St George Illawarra.
"We're pleased to be able to call upon an experienced player with NRL experience at a difficult time with injuries," Rabbitohs interim head coach Ben Hornby said.
Murray's injury will further strengthen Haumole Olakau'atu's Origin case, with the Manly second-rower a strong chance to debut at Accor Stadium.
Angus Crichton could well join him, either starting or off the bench, with the Sydney Roosters second-rower in fine form after starting the year in reserve grade.
Liam Martin and Isaah Yeo are the other backrowers almost certain to appear in coach Michael Maguire's 17 when he reads out his maiden NSW Origin team later this month.
Murray's injury comes as another hit to the Rabbitohs, whose continual setbacks this season resulted in coach Jason Demetriou being axed last Tuesday.
Prop Tevita Tatola, centre Campbell Graham and young winger Tyrone Munro are all sidelined long-term through injury.
Rising star Jye Gray suffered an ankle injury against Penrith, while superstar fullback Latrell Mitchell has missed the past three games through suspension.
Halfback Dean Hawkins suffered a quad injury against the Panthers, while Lachlan Ilias's season is all but over after his leg was broken playing reserve grade.
Winger Alex Johnston is at least due to return from a hamstring injury soon, with Souths taking on St George Illawarra and North Queensland in the next fortnight.
But the loss of Murray comes as another seismic blow to the Rabbitohs' faint hopes of rebuilding their season after one win from their opening eight games.
10°C