Captain and flanker Fraser McReight, backs Josh Flook and Filipo Daugunu and lock Lukhan Salakaia-Loto will miss Saturday's clash with the Western Force for what Kiss terms a "regeneration week".
Hulking prop Massimo De Lutiis will return from a long-term injury to power the pack, while lock Hamish Muller, flanker John Bryant and centre Isaac Henry slot in for the high-profile absentees.
Carter Gordon will wear the No.10 again, starting alongside scrumhalf Louis Werchon, while fullback Jock Campbell will play his 100th Super Rugby game.
Significantly, 50-Test Wallabies halfback Tate McDermott will also return from a long-term hamstring injury and play club rugby this weekend.
The Reds' loss to the Chiefs last Friday all but dashed hopes of a top-three finish and left them just three points clear of the Highlanders in sixth, five points back from the fourth-placed Crusaders.
The top six earn finals berths and the Reds will complete the regular season with a tricky trip to Auckland to face Moana Pasifika, before hosting the Fijian Drua.
It leaves them with a hill to climb, given they'll likely have to create history and win a finals game in New Zealand to even survive into the second week of the post-season.
"Bring on the hill, the boys are saying, that's just the reality," Kiss said.
"The Kiwi teams are the ones with the best form, but we're slowly building.
"We've got a deep enough squad to go over and do the job. This game plus two more, how do you get that right so you're in the right place to be as fresh as possible?
"You've got to make the finals (but) we're trying to be as smart and practical as possible at the same time."
Ben Donaldson pulled the strings in an emphatic defeat of the Reds in Brisbane earlier this season, but is among a list of key omissions for the Perth rematch.
The flyhalf (quad) and prop Tom Robertson (calf) are carrying short-term issues, while in-form scrumhalf Henry Robertson will have surgery to repair his anterior cruciate ligament in a blow to his Test prospects.
Waratahs coach Dan McKellar has made eight changes to his starting side for the trip to Fiji to face the Drua, with Joseph-Aukuso Suaalii retained at outside centre for his third game back from injury.
The Brumbies, two points clear of the Reds in fifth, have a bye.
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