The star fullback has not played at any level since the Rabbitohs' loss to Parramatta on May 19, having tweaked his calf during NSW's camp for the series opener late last month.
The injury forced Mitchell out of Origin camp again last Thursday and on Tuesday Souths confirmed it was still bad enough to rule him out of Sunday's match against North Queensland.
In better news for the Rabbitohs, five-eighth Cody Walker has bounced back from the quad injury that sidelined him last week and will line up.
Ben Hunt has been named to captain St George Illawarra against the Warriors on Friday despite news breaking over the weekend that he had requested an immediate release from the club following its coaching upheaval.
The Queensland representative's availability will likely depend on the amount of game time he is given in Wednesday night's second Origin match.
Dragons forward Jack de Belin returns from the head knock that required him to leave the field on a stretcher in round 15 and will play his 200th NRL game.
Manly are likely to rest State of Origin representative Tom Trbojevic for the round 17 clash against Melbourne on Saturday after naming him in the reserves.
Kaeo Weekes, fullback for last week's big loss to Parramatta, retains the Sea Eagles' number one jersey.
Sydney Roosters five-eighth Luke Keary has been named to face Canberra despite being substituted out of the tight win over Newcastle last Saturday with a jaw injury.
Scans cleared Keary of a fracture, paving the way for his return, while the Roosters also welcome Victor Radley back from his latest suspension.
Dolphins' first-choice halfback Sean O'Sullivan is a chance to play his first game since suffering a pectoral injury in March, having been named in the reserves to face the Eels on Saturday.
Wayne Bennett's side also welcome veteran forward Felise Kaufusi back from the three-match suspension he incurred for a high tackle in round 12.
The Dolphins have named Josh Kerr to play a week after the Dragons granted him an immediate release from the remainder of his contract.
Shaun Lane is in the reserves for Parramatta so could return from his hamstring injury.
Brisbane winger Selwyn Cobbo returns from the hip injury that ruled him out of Origin II and will line up in Sunday's derby clash against Gold Coast, who have five-eighth Kieran Foran back from a toe complaint.
The Warriors' playmaking stocks have been replenished, with Dylan Walker recovering from a toe injury, but Te Maire Martin's leg complaint is set to keep him out for at least another week.
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