South Sydney will be without fullback Latrell Mitchell until Round 21 at the very least, with the Rabbitohs star also set to miss the final game of the 2023 Origin series due to an ongoing calf injury.

Mitchell hasn't played since Souths' Round 12 loss to Parramatta due to the injury, which was sustained during training with New South Wales ahead of this year's Origin opener.

The 26-year-old was a major loss in Brad Fittler's plans, with the Blues losing the opening two matches to Queensland in Mitchell's absence to concede another series to the Maroons.

Rabbitohs coach Jason Demetriou has also been left to call on reinforcements in the wake of Mitchell's latest setback, with the Souths mentor revealing the Bunnies will remain without their explosive No.1 for some time still.

“He won't be available for game three – his calf is not responding – and he won't play until after the bye [in round 21],” Demetriou told reporters on Saturday, via The Sydney Morning Herald. 

“It's taken longer than we thought. With the calf, they can sometimes scan better than they are. We had the same with Hame [Sele] earlier in the year, and we've had similar problems with Jacob Host –the scan says one thing, but the way they respond and are able to train is the opposite.

“We're not in the position where we need to rush it at all. We need to make sure we get Latrell fit and firing for after that bye week.

“[By being conservative] it takes the pressure of him in terms of trying to get on the field here and for Origin, and just focus on his rehab.”

The Rabbitohs are scheduled to face premiership threats Brisbane in Round 21, with the Bunnies having the Cowboys, Warriors and Bulldogs in their sights prior to that match at Sunshine Coast Stadium.

South Sydney will host North Queensland on Sunday at Accor Stadium as they look to return to the winner's list after falling to St George Illawarra in Round 15 prior to their bye.