Coach Clarke Dermody rang the changes after the frustrations of their loss to the Rebels over the weekend.
He was disappointed with the Melbourne result because the Highlanders did enough to win the game but were frustrated by their inability to follow up on their scoring efforts quickly.
"When we'd score, we'd let them in straight away. We didn't create any pressure on them, and were not happy with how the game ended up."
That was a factor in their selection of players against the Reds.
The choice was about how they wanted to play against the Reds, how they set the game up, and how they wanted to finish.
As a result, Oliver Haig was rewarded with the blindside flanker spot for his impressive display against the Rebels, while Billy Harmon moved to No8, with Sean Withy playing the openside flank.
Dermody said the Highlanders players elected Haig as their player-of-the-day by a landslide, in a position he wasn't familiar with.
"He's a better player on the edge, to which his skill set is better suited. We thought it was a mature performance by a young player, and we're excited to see him play at six [blindside flanker].
Hugo Plummer will partner Pari Pari Parkinson at lock.
In the backs, Jonah Lowe's injury has seen centre Tanielu Tele'a called over to join the side. James Arscott will start at halfback, and Cameron Millar has been given the start at first five-eighths.
Conor Garden-Bachop will play at fullback, with Jacob Ratumataivuki-Kneepkens on the bench.
Dermody said, "Conor came on and impacted the game against the Rebels. He played with a lot of freedom and created quite a bit around the counter attack. Jacob hasn't been playing as well as at the start of the season and he has had three yellow cards this year. So, there's a part of the defence wound around those pressure situations that he's working on."
But Dermody said bringing on halfback Folau Fakatava, first five-eighths AJ Faleafaga and Ratumataivuki-Kneepkens in the latter stages would allow the Highlanders to finish strong.
Looking at the Reds, Dermody said they kick a lot and were patient in their kicking game, and Arscott and Millar have been given the job of controlling that.
Arscott said he was looking forward to playing alongside Millar, who he rated as a good kicker.
"I want to get the ball out to the fast backs and play that fast tempo."
Ricky Jackson is starting at hooker, a rare start for him. He said there was healthy competition among the three hookers in the squad, and he was looking forward to the opportunity.
"We're all learning and trying to make our game better for Super Rugby and for the NPC. So, the best we can do is help each other and push each other in training."
As a forward unit, they wanted to get good ball for the backs because if they couldn't get their set piece going, their attack suffered.
"That's my core role and getting that right is key for Friday."
After some messy scrums against the Rebels, they need to be able to adjust to the game and the referees faster and would be looking to achieve that in Brisbane.