The team will travel to Dunedin today and have a light run at the stadium tomorrow night.
Boom openside flanker Liam Gill has been named in the starting 15 after he missed last Saturday's game against the Bulls due to a minor knee complaint.
Also coming back into the side is lock Rob Simmons, while the Reds have a new wing pairing in Luke Korahan and Dom Shipperley. Shipperley is returning from a back injury.
Powerful winger Digby Ioane has not recovered from a bang on the knee and Chris Feauai-Saulia has picked up a thigh strain.
Unavailable for the team this week are hooker Saia Faingaa, who has a sore neck, halfback Nick Frisby, who rolled his ankle at a training on Monday night, and former New Zealand Colt Mike Harris, who has not recovered from a sore hand.
Simmons will lock the scrum with James Horwill for the first time in nearly a year as Horwill continues his comeback from a long-term hamstring injury.
He is expected to get about an hour on Friday night.
The Reds have won four of their six games so far and have the added bonus of having champion halfback Will Genia back in the mix. They defeated the Bulls 23-18 in Brisbane on Saturday night.
Quade Cooper, who is expected to handle the goal-kicking, will be someone for the Highlanders to watch.
It will be Ewen McKenzie's 121st game in charge of a Super rugby franchise, which breaks the record held by Robbie Deans. McKenzie coached the Waratahs from 2003 to 2008 and started with the Reds in 2010.
He coached in France between those times and has signalled he will leave the Reds at the end of the season.
The Reds will not have history on their side when they run out on the stadium on Friday.
They have never won a game against the Highlanders in New Zealand although they have only played the southern team in New Zealand once in the past six years.
That was in 2009 when the Highlanders won 24-19 in Invercargill.