They start their 2017 Super Rugby campaign against the Blues in Melbourne in the first-ever Thursday game.
New recruits Amanaki Mafi, Jackson Garden-Bachop and Jack Maddocks have been named in the run-on team - while home-grown rookie Jordan Uelese and Tyrel Lomax have been included as reserves.
Rebels coach Tony McGahan has named Mafi at No.8, which will see Wallaby back row forward Lopeti Timani paired alongside Steve Cummins, who will make his second start for the franchise, in the locks.
The combination of scrumhalf Nic Stirzaker and flyhalf Garden-Bachop has got the nod the first opening round with Jack Debreczeni to continue at fullback and Maddocks to make his debut on the right wing.
The halves pairing will celebrate milestones - with Stirzaker to record his 50th Super Rugby appearance and Garden-Bachop to become the franchise's 100th capped Rebel.
The Rebels will be without Toby Smith and James Hanson in the front row after the pair suffered injuries in the final trial match against the Reds while Sefa Naivalu will miss the game after failing to overcome an infection.
"A couple injuries and illnesses during the trial phase has impacted selection for our season opener but the situation presents an early opportunity for players to put their hand up and stake their claim for positions," McGahan said.
"It's unfortunate we're missing key players for Round One, we gave everyone the chance to prove their fitness and availability, but it's too early in the season to risk the long term health of our players with a big season still ahead of us."
Substitute hooker Uelese is set to become the third Victorian to make his Super Rugby debut for the Rebels, following Sione Tuipulotu and Rob Leota in 2016, and Jake Schatz is likely to make his Rebels debut off the bench.
The Rebels will have the honour of kicking off the Super Rugby season for the third time in seven years when they host the Blues in the opening game of the season on Thursday.
The head-to-head results favours the Blues 3-2. However, the home side has won all five previous meetings, including a 42-22 Rebels victory when the two sides last met at AAMI Park in 2015.
"There's no shying away from the challenge against the Blues, they're going to be a physical side full of confidence after their trial victory over the Chiefs last week, but we've got 23 fit players ready to roll up their sleeves and eager to impress," McGahan said.
Melbourne Rebels: 15 Jack Debreczeni, 14 Jack Maddocks, 13 Mitch Inman, 12 Reece Hodge, 11 Tom English, 10 Jackson Garden-Bachop, 9 Nic Stirzaker (captain), 8 Amanaki Mafi, 7 Colby Fainga'a, 6 Jordy Reid, 5 Lopeti Timani, 4 Steve Cummins, 3 Laurie Weeks, 2 Pat Leafa, 1 Cruze Ah-Nau.
Replacements: 16 Jordan Uelese, 17 Tom Moloney, 18 Tyrel Lomax, 19 Culum Retallick, 20 Jake Schatz, 21 Ben Meehan, 22 Sione Tuipulotu, 23 Jonah Placid.
Date: Thursday, February 23
Venue: AAMI Park, Melbourne
Kick-off: 19.45 (21.45 NZDT; 08.45 GMT)
Referee: Angus Gardner (Australia)
Assistant referees: Ben O'Keeffe (New Zealand), Will Houston (Australia)
TMO: Ian Smith (Australia)
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