In a completely changed back-line, full-back Shaun Payne returns for the first time since the province's 25-22 defeat to Cardiff on March 1.
This weekend's tie will also see Barry Murphy make his first senior start of the season in the centre alongside Kieran Lewis.
Doug Howlett makes way for Brian Carney on the right wing, while Anthony Horgan will win his 143rd competitive Munster cap on the opposite wing.
In the absence of the injured Ronan O'Gara, Paul Warwick will wear the number 10 jersey, partnered, as he was at the end of the Leinster game, by Tomas O'Leary. Peter Stringer is listed amongst the replacements after recovering from neck and shoulder injuries.
Mick O'Driscoll gets the nod ahead of Donncha O'Callaghan in front of a back row unit of Niall Ronan, Donnacha Ryan and Denis Leamy.
Listed among the replacements are Jeremy Manning and Keith Earls who have both been in excellent form for their respective clubs, Cork Constitution and Garryowen, in the AIB League.
MUNSTER (v Ospreys): Shaun Payne; Brian Carney, Barry Murphy, Kieran Lewis, Anthony Horgan; Paul Warwick; Tomas O'Leary; Federico Pucciariello, Frankie Sheahan,Tony Buckley, Mick O'Driscoll, Paul O'Connell (capt), Donnacha Ryan, Niall Ronan, Denis Leamy.
Replacements: Marcus Horan, Jerry Flannery, Anthony Foley, David Wallace, Peter Stringer, Jeremy Manning, Keith Earls.