The opportunity presents itself because of the injury situation among the backs in the Munster squad. Denis Hurley, Doug Howlett, Ian Dowling, Keith Earls Jean de Villiers and Barry Murphy are all nursing injuries of varying degrees.
But, in pre-season and the British & Irish Cup games, Zebo, Barnes and Cusack have shown what they are capable of and Sunday's step-up at the Sportsground (kick-off 5.05pm) is well within their capabilities.
Zebo was a regular in the Ireland Under-20s' Championship-winning side this season, while Barnes was called into the Irish Under-20 squad last summer for the Junior World Championship in Japan, as was replacement scrum half for Sunday, Conor Murray.
The highly-regarded Cusack has been director of operations for Anthony Foley's British & Irish Cup side, playing a crucial part in their march to the semi-final.
As Munster bid to get back to winning ways in the Magners League, Paul Warwick and Peter Stringer will provide the experience in the backs, with Warwick at inside centre alongside Tom Gleeson and Scott Deasy lining out at full-back.
In all, the Munster management have made twelve changes to the side that overcame Northampton Saints in last Saturday's super-charged Heineken Cup quarter-final. Warwick, O'Driscoll and number 8 James Coughlan are the only survivors.
Up front, loosehead prop Dave Ryan will make his first competitive start for the province, while UL Bohemians lock Dave Foley, Garryowen's Murray and UCC full-back Sean Scanlon could make their senior debuts off the bench.
Munster team manager Shaun Payne said: "There's three games left in the competition. We can't afford to be dropping any points at this stage.
"It's Connacht at the Sportsground. Every year it's a very close game and obviously we came a-cropper there last season, losing 12-6.
"If you look at their recent form, I think they've been outstanding...the best I've seen them play since I've been here (in Ireland).
"I thought they were excellent against Leinster away and deserved to win that game. They did brilliantly to come through last weekend against Bourgoin."
He added: "This is a vital game and there are more to follow this one and obviously with a a challenge like this, the temptation is to pick your frontline team. But we have to take cognisance of what lies ahead and plan accordingly.
"Every single game at this stage of the competition is important. But this one first and it is a question of balancing the books."
MUNSTER (v Connacht): Scott Deasy; Simon Zebo, Tom Gleeson, Paul Warwick, Danny Barnes; Declan Cusack, Peter Stringer; Dave Ryan, Damien Varley, Tony Buckley, Mick O'Driscoll (capt), Billy Holland, Nick Williams, Niall Ronan, James Coughlan.
Replacements: Denis Fogarty, Julien Brugnaut, Dave Foley, Peter O'Mahony, Conor Murray, Jeremy Manning, Sean Scanlon.