Co-captain and fullback Ben Smith has not recovered from the head knock he picked up a week ago against the Force and will sit out the match.
He has been replaced by Matt Faddes, who will make his first competition start in the No15 jersey.
Faddes has played the custodian role over the years but, over the past two seasons at club and provincial level for Otago, has been playing more at centre or on the wing.
With Faddes moving to fullback, Jack Wilson comes into the team on the right wing.
Wilson, the Otago winger, made his debut last month against the Rebels when he scored a try and is making the most of the opportunities he has received when coming into the side because of injuries to others.
First five-eighth Lima Sopoaga is over his groin strain and is back to steer the side around the paddock.
There may have been a temptation to rest the one-test All Black with the team having a bye next week but the coaching staff were keen to get Sopoaga back on the park.
In the pack, loose forward Elliot Dixon has not recovered from a nasty head gash he picked up last week and is replaced by Luke Whitelock.
Shane Christie rotates with Dan Pryor while Joe Wheeler and Mark Reddish will lock the scrum. Christie will also captain the side.
With Brendon Edmonds out for the season because of a knee injury picked up in the rugged game against the Force, Daniel Lienert-Brown comes into the side.
Josh Hohneck and Ross Geldenhuys will be the propping back-up on the reserves bench.
Hohneck has the ability to play on both sides of the scrum.
The Highlanders have the wins well ahead of the Reds this season but do not have the history.
The team last won in Brisbane in 2005. Its suffered a painful last-minute loss when the teams most recently played in Brisbane in 2014.
The Reds side has yet to bag a win this season and sits second last on the table.
Its only positive result from the season is a 25-25 draw with the Blues.
The side, which won the title just five seasons ago, has improved under new coaches Matt O'Connor and Nick Stiles but it still has a way to go to be competitive.
It does welcome back skipper and captain James Slipper, who will make his first start of the season.
Slipper had a slow start to the season because of a delayed return from shoulder surgery.
The Reds had a bye last week so will be well rested for the Highlanders.
Highlanders v Reds
Brisbane, tomorrow, 9.40pm
Highlanders: Matt Faddes, Jack Wilson, Malakai Fekitoa, Rob Thompson, Patrick Osborne, Lima Sopoaga, Aaron Smith, Liam Squire, Shane Christie (captain), Luke Whitelock, Joe Wheeler, Mark Reddish, Siosiua Halanukonuka, Liam Coltman, Daniel Lienert-Brown:
Reserves: Ash Dixon, Ross Geldenhuys, Josh Hohneck, Tom Franklin, Dan Pryor, Fumiaki Tanaka, Hayden Parker, Jason Emery.
Reds: Karmichael Hunt, Chris Feauai-Sautia, Samu Kerevi, Anthony Fainga'a, Eto Nabuli, Jake McIntyre, Nick Frisby, Jake Schatz, Liam Gill, Hendrik Tui, Rob Simmons, Cadeyrn Neville, Greg Holmes, Andrew Ready, James Slipper.
Reserves: Saia Fainga'a, Sef Fa'agase, Sam Talakai, Ben Matwijow, Curtis Browning, Scott Gale, Sam Greene, Ayumu Goromaru.
