The dynamic loose forward will miss the remainder of Super Rugby, having sustained a stress fracture in his leg.
He is one of two players missing due to injury for the side’s final Super Rugby Aotearoa match, against the Hurricanes in Wellington tomorrow.
Ngane Punivai will also miss the game, having suffered bleeding in a quadriceps.
The versatile back has been replaced by Sam Gilbert on the right wing, who returns after a nine-month injury layoff himself.
Hugh Renton replaces Mikaele-Tu’u on the bench.
Loosehead prop Ethan De Groot switches into the starting line-up for Ayden Johnstone in the only other change from the side which beat the Blues two weeks ago.
Highlanders coach Tony Brown said it was disappointing to lose Mikaele-Tu’u, who is the side’s eighth player ruled out for the season.
"It’s a bit consistent with the rest of our guys," he said.
"We seem to be losing two guys a week on average at the moment.
"It’s a big disappointment for him, so hopefully he can come back and have another good [NPC]."
He said it was good to have Gilbert back, the young outside back having had his introduction to the side a year ago.
Brown said the 22-year-old was a more natural fullback, although the side was just keen to get him on the field.
While tomorrow’s game may be meaningless in terms of making the competition final, the Highlanders were focused on it and not the looming transtasman competition.
They have yet to claim back-to-back wins, although doing so will ensure they finish the Aotearoa competition with a win over each team.
There had been games among those lost — notably the Chiefs at Forsyth Barr Stadium — that the side had let slip away, which
left Brown with a feeling of disappointment.
"We haven’t done that [won back-to-back games] yet.
"But for us, whatever happens against the Hurricanes it’s going to be one of those campaigns where we lost a couple of games that we shouldn’t have.
"It’ll always be the disappointing thing at the end of this campaign . . . that we should be in the final."
The Hurricanes have made two changes to the side that was pipped by the Chiefs a week ago.
Powerful winger Julian Savea returns to the No 14 jersey, while Billy Proctor is promoted to the bench at centre.
Kickoff is at 7.05pm.
