Connacht head coach Pat Lam has named 21-year-old fly-half Jack Carty in his starting lineup to take on Glasgow Warriors on Sunday.
Carty will play alongside scrum-half Kieran Marmion who earned his first Ireland Wolfhounds cap in the victory over England Saxons during the PRO12 break.
Craig Ronaldson returns from injury to partner Galway-born Eoin Griffin in the centres while Ireland international Robbie Henshaw has been released back to his province to start at full-back this week in place of the injured Gavin Duffy.
Fionn Carr starts on the right wing for his 100th league game while Connacht's joint top try scorer of the season (with Marmion) Matt Healy is named on the left.
Up front, Roscommon-born prop Denis Buckley secures his first start of the season in an all new front row with Rodney Ah You and Jason Harris-Wright.
Andrew Browne moves into the second row to partner the incoming Mick Kearney. John Muldoon captains the side from a back row berth with Jake Heenan and George Naoupu.
"It's obviously a big disappointment for us losing Craig (Clarke), (Nathan) Whitey, Sean (Henry) and Brett (Wilkinson) - four of the front-liners from our forward pack," said Lam.
"But we have full confidence in our squad and this is another opportunity for our younger forwards to step up, with a start this week.
"Having Robbie (Henshaw) back in the starting XV is a bonus, especially with Gavin (Duffy) unavailable this week. The versatility of our young backs allows Robbie to move to full back and Craig (Ronaldson) to slip into inside centre with Eoin (Griffin) moving outside him.
"Playing Glasgow is a huge test for us. They are a very direct side with one of the best defensive structures in the entire league. Connacht has never won at Scotstoun and this is something we want to change."
Meanwhile, Warriors boss Gregor Townsend has handed first starts to wingers Lee Jones and Rory Hughes.
Jones arrived this week on loan until the end of the season, having been released to the club from Scotland 7s duty in New Zealand.
21-year-old Hughes joined the club in the summer of 2013 as part of the Elite Development Programme and has been on good form for Stirling County in the Premiership.
After starting on the wing against Toulon in the Heineken Cup last month, Niko Matawalu moves to full-back.
Richie Vernon starts his first game at centre, since switching positions from the back row, and will partner Mark Bennett in midfield.
Ruaridh Jackson has been released from the Scotland squad and starts at fly-half, with Henry Pyrgos wearing the number nine jersey, after signing a new one-year deal with the club this week.
Gordon Reid starts at loosehead and Ed Kalman is at tighthead, while Pat MacArthur also comes back from Scotland duty and takes his place at hooker.
Leone Nakarawa and Tom Ryder are in the engine room, with Rob Harley at blindside and Tyrone Holmes at openside. Josh Strauss returns to the side after missing the Toulon game through injury and will captain the team at number 8.
Former Warriors Elite Development scrum-half, Murray McConnell is named amongst the replacements, having been in great form for his club side Ayr this season.
"Connacht are an extremely tough side to play and it was a very close game when we played them in over in Galway in November, so we know we face a real challenge on Sunday," said Townsend.
"International call-ups and injuries during this period of games shows how important it is to put together a strong squad with real depth.
"Last season during the Six Nations our players stepped up and performed really well, so we expect those involved on Sunday to seize their opportunity.
"We were delighted to get Lee Jones in this week and he is a player who has impressed in the international set up and is a proven try scorer. He gets an early opportunity to play for the club and it's a great chance for him to do what he does best in front of our home supporters.
"Rory Hughes has impressed all season in training and has come close to playing a few times. He's worked hard on his game and performed well for Stirling County, so we're looking forward to seeing him in a Warriors jersey.
"We've been keeping an eye on a number of young Scottish club players and Murray McConnell is one who has been working extremely hard and fully deserves to be involved this weekend."
Form: Glasgow Warriors last two fixtures at Scotstoun in the PRO12 have both fallen foul of the weather, whilst the Warriors have now won at the venue since a 20-16 victory over Exeter in the European Cup on 20 October. Glasgow have won three of their last four home games against Irish provinces. Connacht's solitary win the PRO12 since Round 1 was 14-11 at home to the Dragons in Round 10. Connacht's most recent away victory in the tournament was 32-24 against Edinburgh at Murrayfield on 12 April. The Warriors have won their last four contests against Connacht, whilst the Irishmen's only two victories on Glasgow soil came at Hughenden in September 2003 and Firhill in September 2010.
Glasgow Warriors: 15 Niko Matawalu, 14 Lee Jones, 13 Richie Vernon, 12 Mark Bennett, 11 Rory Hughes, 10 Ruaridh Jackson, 9 Henry Pyrgos, 8 Josh Strauss, 7 Tyrone Holmes, 6 Rob Harley, 5 Tom Ryder, 4 Leone Nakarawa, 3 Ed Kalman, 2 Pat MacArthur, 1 Gordon Reid
Replacements: 16 Dougie Hall, 17 Jerry Yanuyanutawa, 18 Jon Welsh, 19 James Eddie, 20 Fraser Brown, 21 Murray McConnell, 22 Finn Russell, 23 Scott Wight
Connacht: 15 Robbie Henshaw, 14 Fionn Carr, 13 Eoin Griffin, 12 Craig Ronaldson, 11 Matt Healy, 10 Jack Carty, 9 Kieran Marmion, 8 George Naoupu, 7 Jake Heenan, 6 John Muldoon, 5 Andrew Browne, 4 Mick Kearney, 3 Rodney Ah You, 2 Jason Harris-Wright, 1 Dennis Buckley
Replacements: 16 Dave Heffernan, 17 Ronan Loughney, 18 JP Cooney, 19 Michael Swift, 20 Aly Muldowney, 21 Paul O'Donohoe, 22 Dan Parks, 23 Darragh Leader
Date: Sunday, February 9
Kickoff: 14:00 GMT
Referee: Leighton Hodges (Wales)
Assistant referees: Neil Paterson (Scotland), Graeme Marshall (Scotland)
Citing Commissioner: John Montgomery (Scotland)