Connacht coach Michael Bradley has made four changes to the team that started the province's last game - their 66-0 Amlin Challenge Cup win over Olympus Rugby Madrid on January 23.
Liam Bibo drops to the bench as Duffy is reinstalled at full-back and Troy Nathan moves to the right wing. The rest of the back-line is unchanged, with scrum half Frank Murphy having recovered from a calf injury.
With Miah Nikora out of action, Nathan will also provide cover for Ian Keatley at out-half.
There are three changes up front. Brett Wilkinson replaces Ronan Loughney at loosehead prop, Bernie Upton comes in for Mike McCarthy in the second row and Johnny O'Connor makes way for Ray Ofisa at openside flanker.
Bradley said: "Over the last couple of years it has been difficult for us going to Wales, but around this time of the year we would perceive ourselves as having a bit of an advantage on sides that have a lot of international commitments.
"If we start well and maintain our defence, along with the feel-good factor from the Amlin Challenge Cup, we could go well against the Ospreys but it will be difficult."
CONNACHT (v Ospreys): Gavin Duffy; Troy Nathan, Niva Ta'auso, Keith Mathews, Fionn Carr; Ian Keatley, Frank Murphy; Brett Wilkinson, Sean Cronin, Robbie Morris, Michael Swift, Bernie Upton, John Muldoon, Ray Ofisa, George Naoupu.
Replacements: Adrian Flavin, Jamie Hagan, Mike McCarthy, Johnny O'Connor, Conor O'Loughlin, Adian Wynne, Liam Bibo.