Ireland scrum-half Kieran Marmion will start for Connacht against Grenoble, while centre Robbie Henshaw returns to outside centre for their Challenge Cup quarter-final on Saturday (8.05pm, live on RTÉ Radio 1).
Marmion missed the Pro12 defeat to Ulster last Friday with a quad injury, while Henshaw was at full-back.
The changes are among five personnel and seven positional switches for Pat Lam’s men.
Shane O'Leary, who spent the 2013/14 season playing with the French opponents, will make his third start for Connacht at out-half.
Up front, recent Ireland international debutants Finlay Bealham and Ultan Dillane start for the first time since their Six Nations involvement.
The back row is reshuffled and features three Galway-born players with Sean O'Brien from the academy coming in to start at blindside flanker.
All checked in and ready for our journey to Grenoble (via Geneva) #ChallengeCup #RoadToEurope pic.twitter.com/DnYwLszDDx
— Connacht Rugby (@connachtrugby) April 8, 2016
Eoin McKeon once again moves to openside, while John Muldoon captains the side wearing the number 8 shirt.
Jake Heenan rolled his ankle in Tuesday’s training session and has not travelled with the squad.
Lam said: "We understand the challenge we face travelling to play a confident Grenoble side in their home ground. But this is knock-out rugby and we are determined to bring a semi-final home to the Sportsground for our supporters.
"With two teams looking to play an attacking style of rugby, it will come down to the small margins in defence and who can take their opportunities. It's set up to be a really entertaining game and we're really looking forward to it."
Connacht: Matt Healy, Niyi Adeolokun, Robbie Henshaw, Bundee Aki, Danie Poolman, Shane O'Leary, Kieran Marmion; Denis Buckley, Tom McCartney, Finlay Bealham, Ultan Dillane, Andrew Browne, Sean O'Brien, Eoin McKeon, John Muldoon (captain).
Replacements: Dave Heffernan, Ronan Loughney, JP Cooney, Quinn Roux, James Connolly, John Cooney, Peter Robb, Fionn Carr.
Here is the team that will face @connachtrugby https://t.co/q2tzjFtJW8 #FCG #FCGCR pic.twitter.com/tf8WavOqKj
— FC Grenoble Rugby (@FCGrugby_en) April 8, 2016
