Rabbitohs halfback Adam Reynolds has been sidelined indefinitely with a back fracture suffered in last week's loss to Parramatta.
South Sydney coach Wayne Bennett confirmed Reynolds would miss Friday night's clash with Newcastle and would only return when he is pain-free.
"He won't be playing - he's got a small fracture in his back from last weekend's game," Bennett said.
"It's serious enough that he can't play but it's not something that will be two or three months, it's just when his pain-free he'll be able to play again because he's not pain free at the moment."
Bennett said the halfback incurred the injury early in the loss to the Eels after copping a knee in the back.
"He got up very slow and very sluggish but he managed to get through the game. No-one's sure how he did that," Bennett added.
"He was obviously in a lot of pain and x-rays showed later on, scans showed he's got a small fracture in the lower back.
"He'll be out as long as he's in pain so we don't know if it will be a month, three weeks, six weeks, five weeks. But there's no surgery required. When he can run and handle the pain he'll be right to play."
Bennett said he would rest NSW five-eighth Cody Walker from Friday's match, with fellow State of Origin stars Dane Gagai, Damien Cook and Cameron Murray likely to back up from the series opener.
"Cody Walker won't play but the others will," Bennett said.
"I just don't think it's in his best interests to back up two days later when he hasn't played before at this level. He's got a couple of niggles so it's about making sure he's fit to play next week."
With both starting halves missing for Souths, Adam Doueihi will start at halfback with Connor Tracey to line up at five-eighth against the Knights, Bennett confirmed.