There was hope Sopoaga, who hasn't played since picking up a hamstring injury against the Blues in round three, would return to play the Stormers in Dunedin in Friday night.
However, Sopoaga will sit out a seventh consecutive game, meaning Marty Banks will again run the show and Fletcher Smith will provide cover off the bench.
Sopoaga is joined on the sidelines by loose forward Luke Whitelock, who has been struck down by concussion-type symptoms on the back of the Highlanders' 40-15 win against the Sunwolves last weekend.
Fellow loose forward Elliot Dixon, a late scratching against the Sunwolves due to a knee infection, will also miss Friday's match.
The loss of Dixon and Whitelock leaves five Highlanders loose forwards on the injury list, with Dan Pryor, Shane Christie and James Lentjes also still unavailable.
Gareth Evans and Dillon Hunt will start at blindside and openside flanker respectively against the bulky Stormers, who will no doubt be hurting after the Crusaders walloped them 57-24 last weekend.
In a couple of tweaks to the backline, winger Patrick Osborne returns to start on the left-wing in place of Tevita Li, in what will be his 50th Super Rugby game for the Highlanders.
Malakai Fekitoa has reverted back to his preferred centre position, while second-five eighth Rob Thompson will make his first appearance since a family bereavement last month.
Utility back Richard Buckman is unavailable due to injury and will miss his second game on the trot.
After playing their sixth home game of the season on Friday, the Highlanders will head to South Africa to play the Cheetahs in the first of three consecutive overseas away games.
Following the Cheetahs, they will play the Bulls in Pretoria and the Western Force in Perth, in what is typically a tricky assignment for Kiwi teams on their way home.
AT A GLANCE
Highlanders: Ben Smith (c), Waisake Naholo, Malakai Fekitoa, Rob Thompson, Patrick Osborne, Marty Banks, Aaron Smith, Liam Squire, Dillon Hunt, Gareth Evans, Tom Franklin, Alex Ainley, Siosuia Halanukonuka, Liam Coltman, Daniel Lienert-Brown. Reserves: Greg Pleasants-Tate, Aki Seiuli, Siate Tokolahi, Joe Wheeler, Jackson Hemopo, Kayne Hammington, Fletcher Smith, Matt Faddes.
Photo by: ROB JEFFERIES/GETTY (Highlanders pivot Lima Sopoaga will miss a seventh consecutive game with a hamstring injury).