The 21-year-old Galwegians clubman slots into the front row alongside Brett Wilkinson and Jamie Hagan, while Michael Swift and Bernie Upton renew their second row partnership.
In all, Connacht boss Eric Elwood has made six changes in personnel to the side that securing a losing bonus point in Treviso in their last league game.
Mike McCarthy moves into the back row to cover for the injured Ray Ofisa, allowing New Zealander Upton to return at lock.
In the backs, Troy Nathan gets the right wing berth ahead of Darragh Fanning, and Miah Nikora and Frank Murphy return at half-back.
The 20-year-old Eoin Griffin, who was the man-of-the-match in the Samoa game, gets a chance to impress in midfield alongside Keith Matthews. He comes in for the injured Niva Ta'auso.
Friday's match will mark full-back Gavin Duffy's 100th competitive appearance for his native province. The Mayo man made his senior debut for Connacht against Cardiff back in 2001.
Having been released from the Ireland squad this week, Duffy will join the elite group of Connacht centurions which includes his current coach Elwood and and team-mates Swift and Wilkinson.
CONNACHT (v Ospreys): Gavin Duffy; Troy Nathan, Eoin Griffin, Keith Matthews, Fionn Carr; Miah Nikora, Frank Murphy; Brett Wilkinson, Dermot Murphy, Jamie Hagan, Michael Swift, Bernie Upton, Mike McCarthy, Johnny O'Connor, John Muldoon (capt).
Replacements: Ronan Loughney, Barry Fa'amausili, Dylan Rogers, Andrew Browne, Ezra Taylor, Cillian Willis, Ian Keatley, Darragh Fanning.