O'Gara, Earls, Leamy and O'Connell all saw action in Ireland's RBS 6 Nations victory over England last weekend.
In explaining what is undoubtedly a big call at scrum half, Munster head coach Tony McGahan said: "Conor has been a consistent member of the senior squad in training over the past twelve months because of international call-ups and injuries in our half-back position.
"In this time he has gathered valuable training experiences from the more senior players in the squad which allowed him to play off the bench in the last Six Nations window and start against the Dragons in our most recent Magners League game.
"He impressed the coaching staff and fellow players with an enthusiastic and mature display in his first professional start.
"He deserves to be in the mix competing with Peter (Stringer) and Duncan (Williams) for game-time with Tomas (O'Leary's) unfortunate bout of injuries."
All in all, McGahan has made ten changes to the starting line-up from the win over the Dragons at Musgrave Park three weeks ago. One of those changes is forced by Paul Warwick's return to Australia on family matters.
Elsewhere, the inclusion of the fit-again Felix Jones at full-back sees Johne Murphy switch to outside centre with Earls resuming the left wing in place of Simon Zebo.
Up front, it is all change in the front row with Wian du Preez, Damien Varley and Tony Buckley starting on this occasion.
O'Connell comes in for Ian Nagle in the second row, while the back row is unchanged apart from the inclusion of openside flanker Niall Ronan, who returned from injury in the 'A' game against Ulster Ravens last week.
MUNSTER (v Cardiff Blues): Felix Jones, Doug Howlett, Johne Murphy, Lifeimi Mafi, Keith Earls; Ronan O'Gara, Conor Murray; Wian du Preez, Damien Varley, Tony Buckley, Paul O'Connell (capt), Mick O'Driscoll, James Coughlan, Niall Ronan, Denis Leamy.
Replacements: Mike Sherry, Marcus Horan, Stephen Archer, Donnacha Ryan, Peter O'Mahony, Peter Stringer, Sam Tuitupou, Declan Cusack.