Coach Michael Bradley has made one change to the side that lined out against the Queensland Reds in Connacht's final pre-season friendly.
The fit-again John Hearty comes into the starting line-up on the left wing as Connacht bid to continue their proud record of having won their opening league match every year since the competition began in 2001.
Muldoon will become the eleventh player to reach the century milestone of caps for the province.
South African-born prop Brett Wilkinson, now beginning his third season with the westerners, will be making his 50th appearance.
Notably, full-back Fionn Carr, half-backs Ian Keatley and Frank Murphy and hooker Sean Cronin, all summer recruits, will make their competitive debuts for Connacht from the off. Experienced scrum half Kieran Campbell could also make his bow off the replacements bench.
CONNACHT (v Ospreys): Fionn Carr; Liam Bibo, Gavin Duffy, Keith Matthews, John Hearty; Ian Keatley, Frank Murphy; Brett Wilkinson, Sean Cronin, Robbie Morris, Mike McCarthy, Andrew Farley, John Muldoon (capt), Ray Ofisa, Colm Rigney.
Replacements: Adrian Flavin, Ronan Loughney, Andrew Browne, Michael Swift, Kieran Campbell, Troy Nathan, Aidan Wynne.