Captain Ben Smith, No8 Luke Whitelock, loose forward Shannon Frizell and hooker Liam Coltman will all miss the game while Aaron Smith will start from the bench.
Waisake Naholo will start on the right wing while flanker Dillon Hunt missed the All Black squad so is not liable for the resting policy. Loose forward Liam Squire has missed a big part of the season because of a thumb injury but comes on to the reserves bench.
Interim head coach Mark Hammett said the side would have finished its All Black commitments after the game.
"This is part of the rest agreement and we wanted to reduce the disruptions in what has been a disruptive week anyway," Hammett said.
"Then we want to maintain combinations as much as possible. I think we have managed to do that. We are starting seven out of the eight forwards who played against the Tahs and but for an elbow injury to Elliot [Dixon] he would have been there."
Hammett said good management had allowed the team to get the players their rests without being too disruptive on the team.
"We have been fortunate that we have managed Aaron Smith really well. We have been in communication with the All Blacks and have managed his minutes. We were fortunate in we had two early byes."
The side was looking forward to welcoming back Squire, who broke his thumb in early March and would start off the bench.
Hammett said Squire was a more experienced player which was helping him in his latest comeback.
"As you get older you get a bit more experienced and injuries are part of the game. Liam has learnt to handle that more."
No8 Marino Mikaele Tu'u makes his first start for the Highlanders and James Lentjes will make a rare start on the blindside flank.
Josh McKay starts at fullback, another debut for the side.
"Josh has been working really hard behind the scenes and has been really good in club footy. I know it is a different level but he had worked really hard for it.
"This opportunity has been waiting for him. We are really rapt for him."
Richard Buckman is in the reserves and is set to play his first game of the season. He played premier two grade last week as his club University lost to West Taieri.
The Reds have been rocked by the suspension of their skipper, James Slipper, who has been banned for two months for testing positive for cocaine.
Highlanders v Reds
Brisbane, tomorrow, 9.45pm
Highlanders: Josh McKay, Waisake Naholo, Rob Thompson, Tei Walden, Tevita Li, Lima Sopoaga, Kayne Hammington, Marino Mikaele Tu’u, Dillon Hunt, James
Lentjes, Tom Franklin, Jackson Hemopo, Tyrel Lomax, Ash Dixon (captain), Daniel Lienert-Brown. Reserves: Greg Pleasants-Tate, Aki Seiuli, Kalolo Tuiloma, Josh Dickson, Liam Squire, Aaron Smith, Josh Ioane, Richard Buckman.
Reds: Hamish Stewart, Izaia Perese, Samu Kerevi, Duncan Paia’aua, Jordan Petaia, Jono Lance, Ben Lucas, Scott Higginbotham (captain), George Smith, Angus Scott-Young, Harry Hockings, Izack Rodda, Taniela Tupou, Brandon Paenga-Amosa, JP Smith. Reserves: Andrew Ready, Sef Fa’agase, Ruan Smith, Kane Douglas, Caleb Timu, Liam Wright, Moses Sorovi, Aidan Toua.