Fresh off their 83-17 demolition of the Sunwolves in Tokyo, the Hurricanes host the Rebels in Wellington on Saturday.
The star trio are among four changes to the starting XV. The other sees Reed Prinsep come in at No 8 to for the injured Blade Thomson.
Hurricanes hooker and captain Coles and first-five Barrett swap places with Ricky Riccitelli and Otere Black respectively after coming off the bench in Tokyo.
Milner-Skudder has recovered from the hamstring strain that ruled him out of the season opener to replace Jordie Barrett at fullback. He will play his first Super Rugby match since March last year.
Hurricanes coach Chris Boyd said the changes had been well mapped out to counter the early season travel.
"Dane and Beauden were always going to come back into the starting team and Nehe would have started round one if he'd been fit, so the selections certainly aren't form related," Boyd said.
"Blade Thomson dislocated his shoulder in Japan and is having scans to determine the severity of his injury, so Reed gets an early chance to stake a claim at the back of the scrum."
Boyd said the challenge for his defending champions was to take their game to another level of intensity.
"We certainly took some positives away from our first match, but I think there is a realisation among the group that this week represents a big step up and we are expecting the Rebels to be highly motivated after their loss to the Blues," he said.
There is one further personnel change to the Hurricanes team with lock Mark Abbott, who was unavailable for the trip to Japan due to a personal commitment, joining Riccitelli, Black and Jordie Barrett in the reserves.
HURRICANES: Nehe Milner-Skudder, Vince Aso, Matt Proctor, Ngani Laumape, Julian Savea, Beauden Barrett, TJ Perenara; Reed Prinsep, Ardie Savea, Brad Shields, Michael Fatialofa, James Blackwell, Jeffery To'omaga-Allen, Dane Coles (c), Chris Eves. Reserves: Ricky Riccitelli, Ben May, Mike Kainga, Mark Abbott, Callum Gibbins, Chris Smylie, Otere Black, Jordie Barrett.
Photo: FAIRFAX NZ (Nehe Milner-Skudder returns to Super Rugby for the first time in almost a year with a starting role for the Hurricanes against the Rebels).