The home team includes new caps Tyrel Lomax, Pari Pari Parkinson, Shannon Frizell, Josh Ioane and Tevita Nabura in the starting side and prop Kalolo Tuiloma and outside back Josh McKay on the bench.
Injury replacement players Terrance Hepetema (centre) and Marino Mikaele Tu'u (loose forward) will get their chance to impress, while several Otago and Southland representative players round out the 32.
Ioane gets the nod at first five-eighth ahead of Fletcher Smith and it will be interesting to see how he goes in the crucial position, while former All Black John Timu's son, Josh Timu, gets a start on the right wing.
The team will be captained by Ben Smith with co-captain Ash Dixon coming off the bench.
Highlanders coach Aaron Mauger said he was looking forward to the contest and what it would deliver.
''There is plenty of competition within the team,'' he said.
''Some guys there who have a bit of experience and then there are some new guys. We'll see how they go in the next couple of games and learn a bit about them.''
The Darryl Gibson-coached Waratahs bring a 27-man team featuring new signing and Australian outside back Curtis Rona, who will play his first match for the Waratahs.
Gibson has also named Wallabies prop Paddy Ryan, fellow front-rower Tom Robertson, utility forward Ned Hanigan and winger Taqele Naiyaravoro.
The two teams have met regularly during the pre-season in recent years with the Highlanders running out a 40-35 winner in Queenstown in 2016.
The game will be played in three 30-minute periods at the Queenstown Recreation Ground. The Highlanders are expected to give everyone a run.
Kick off is at 6pm.