Notably, All Black Aaron Smith is in bubble wrap this week. He is taking one of the two mandatory breaks to freshen up for the international campaign later this year.
That means Kayne Hammington will get a start at halfback, and Josh Renton comes on to the bench.
"We knew at the start of the year we were going to have to use our squad and we have confidence in the guys that are playing those roles," coach Aaron Mauger said.
"Kayne has played well this year and it is exciting for Josh Renton to come back into the 23 as well."
There are three changes in the starting pack. Daniel Lienert-Brown switches with Aki Seiuli, and Elliot Dixon and James Lentjes replace Shannon Frizell and Dillon Hunt respectively.
Frizell announced his arrival last month with a barnstorming effort against the Blues at Eden Park. He scored three tries and the social networks were abuzz with talk of his potential.
But Dixon has been given the starting spot at blindside and powerful Alhambra-Union loosie Marino Mikaele Tu'u comes on to the bench.
"We think Shannon has had an awesome five or six weeks, so it is just a chance for him to freshen up and reflect.
"We bring Marino into the mix. He has been outstanding through training and performed really well for his club and also for the Bravehearts."
Hunt is being rested after a heavy workload.
"He was one of the standouts on tour, even in the weekend against the Sharks where we didn't win the physical battle, his output throughout the game was outstanding."
Out wide, Tevita Nabura replaces Sio Tomkinson, who drops to the bench.
University lock Josh Dickson has been named on the bench. He will bring some much-needed fresh legs.
The Highlanders are coming off a disappointing 38-12 loss to the Sharks in Durban. The side lacked energy and the long flight home and the short turnaround before game against the Lions is not ideal.
But Mauger said the team was excited to be home and preparing for a game under the roof.
"It has been pretty light [week] but the energy has been good and the attitude ... is where it needs to be.
"We come up against a really good Sharks side and they were in great form. We were 14-0 down early in the game and did not quite recover.
`But as we see with this team every week, we certainly did not give up."
The Lions are more expansive than some South Africa teams and should enjoy playing under the roof. But they also have strong set pieces and will look to deny the Highlanders possession.
"I think they are a really dangerous side. They score a lot of tries.
"They have a big forward pack, they kick well and, in the last three or four years, they play a lot of rugby as well, so they are a dangerous side with the ball in hand."