In what was the opening of the new Sydney Football Stadium and brought with a sell out crowd, Murray would attempt to make a tackle on Roosters' winger Kevin Naiqama as he brought the ball out of his own end.
Murray ultimately ended with his head in an awkward position, collecting the hip of the powerful Roosters' winger.
The lock forward went to ground and was quickly taken from the field by South Sydney head trainer Eddie Farah, with immediate concerns raised over Murray's concussion history.
"Cam Murray gone for the game," Fox Sports sideline reporter Matt Russell said in confirming the news that he would be ruled out of the game.
"It was a Cat 1. His second knock for the season."
It was a similar time into the State of Origin decider this year when playing for the New South Wales Blues which ended Murray's night, with a concussion forcing him out just a minute into the contest, which was ultimately won by the Queensland Maroons.
While finals fixtures are yet to be confirmed, it's believed the Roosters and Rabbitohs will have a long turn around before playing the second elimination final as sixth and seventh place next Sunday afternoon, once again at Moore Park.
The long turnaround of eight days could mean Murray is able to take his place in the team, however, he will need to pass through concussion protocols this week.