In a major blow for the southern franchise, medical staff deemed captain Cowan hadn't recovered sufficiently from an elbow injury suffered in the first-round loss to the ACT Brumbies last weekend.
Sean Romans will start at halfback with Cowan's brother Scott coming onto the reserve bench.
Likewise, prop Mackintosh was still feeling a knock to the knee and his place at loosehead goes to Chris King, with Anthony Perenise onto the bench.
Centre Jason Shoemark will be captain, having filled the role for the last 50 minutes against the Brumbies after Cowan and Mackintosh had both left the field.
The only other possible change from last week is on the left wing, where Fetu'u Vainikolo has been bracketed with Kendrick Lynn.
Vainikolo is under investigation by the New Zealand Rugby Union after an early morning incident at a Dunedin bar last Saturday morning.
A misconduct hearing is expected to take place this week.
The teams for the Super 14 rugby match at Wellington on Friday:
Highlanders: Israel Dagg, Ben Smith, Jason Shoemark, Johnny Leota, Fetu'u Vainikolo/Kendrick Lynn, Daniel Bowden, Sean Romans, Steven Setephano, Alando Soakai, Adam Thomson, Hayden Triggs, Josh Bekhuis, Clint Newland, David Hall, Chris King. Reserves: Jason Rutledge, Anthony Perenise, George Naoupu, Tim Boys, Scott Cowan, Jayden Hayward, Lynn/ Brett Mather
Hurricanes: Cory Jane, David Smith, Tamati Ellison (captain), Jason Kawau, Hosea Gear, Daniel Kirkpatrick, Piri Weepu/Alby Mathewson, Victor Vito, Scott Waldrom, Faifili Levave, Jason Eaton, Jeremy Thrush, Neemia Tialata, Dane Coles, John Schwalger. Reserves: Ged Robinson, Jacob Ellison, Api Naikatini, Karl Lowe, Mathewson/Willie Ripia, Ma'a Nonu, Conrad Smith
