Keaon Koloamatangi is suspected to have broken his eye socket in his side's Round 15 loss to the Bulldogs.
The news was confirmed by his coach Wayne Bennett in the Rabbitohs post-match press conference on Sunday night.
In a high-contact collision that was originally thought to be a concussion, Koloamatangi was forced off the field to complete a HIA.
Despite successfully passing the HIA, the 27-year-old was unable to return to the field of play due to the damage done to his eye.
Koloamatangi was originally supposed to head to Perth after the match to join the Blues as part of their extended squad.
Due to the injury, he will now stay in Sydney with Laurie Daley forced to look elsewhere for depth in their forwards ahead of State of Origin Game II.
Many believed the Rabbitohs enforcer had done enough to earn a spot in the Blues 17 after the incumbent prop Mitch Barnett went down to a knee injury and has since been ruled out for the season.
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The setback has significant implications on the Origin series, however, the greater disappointment will be for the South Sydney faithful who have watched their side be ravaged by injury.
Koloamatangi will go for scans and be hoping that he can return to action as soon as possible, with the Rabbitohs still within striking distance of finals football.