Hamstring injuries to Jamie Humphreys and Cody Walker have left Mitchell to partner Jayden Sullivan in South Sydney's halves to face North Queensland in Perth on Saturday.
It means Mitchell will go a second-straight week out of his preferred fullback spot, having returned from injury to start in the centres last week.
But coach Wayne Bennett had few options for this week's game, given a NSW Cup suspension has denied big-money recruit Lewis Dodd the chance for a debut, and Josh Schuster is still working back to fitness.
Bennett has received a boost in his outside backs, though, as Alex Johnston and Euan Aitken return from injury, with the former resuming his pursuit of the NRL's all-time try-scoring record.
Fighting to ignite their season, the Panthers have finally called on Talagi to start in the halves opposite Nathan Cleary for Thursday's match against the Dolphins.
The most-hyped external recruit of the Penrith dynasty has been restricted to only one game from the bench through five rounds but replaces five-eighth Jack Cole, who suffered a head knock in Penrith's fourth-straight loss last week.
Brad Schneider is listed on the bench as cover and may spend some time at hooker as Mitch Kenny's shoulder issue rules him out.
Luke Sommerton has been named to start at No.9 in only his sixth NRL game, while fullback Dylan Edwards returns from a groin issue.
Towering rookie Hugo Savala will replace Townsend in the Sydney Roosters' halves to face Brisbane on Friday following a disappointing start to the season for the veteran recruit.
Savala, who only made his NRL debut in round two, lines up next to Sandon Smith as the Roosters look to recover from a dismal 1-4 start.
Winger Dom Young has so far been spared the axe amid speculation he too could be dropped.
But Mark Nawaqanitawase is a chance for a late charge into the backline after being named 18th player on return from a calf issue.
Newcastle have opted to push Phoenix Crossland from hooker to halfback rather than recall out-of-favour Jackson Hastings for the clash with Wests Tigers.
Jack Cogger (finger) and Tyson Gamble (back) are unavailable to partner five-eighth Fletcher Sharpe and Will Pryce has been recently released from his deal to return to England.
Former Super Rugby player Tyrone Thompson, brother of Knights prop Leo, will make his NRL debut as Jacob Saifiti (calf) and Jack Hetherington (shoulder) drop out of the forward pack.
Kyle McCarthy plays his second NRL game on the wing replacing James Schiller (head knock), with Matt Arthur, son of former Parramatta coach Brad, makes his club debut from the bench.
Jeral Skelton and Jarome Luai respectively return from a hamstring issue and suspension to bolster the Tigers.
Reuben Cotter is back from illness for the Cowboys' clash with Souths, while Zac Lomax's move to the wing has been confirmed for Parramatta's match against Canberra in Darwin.
