He said: "It is an honour to face Ireland in my first test as Eagles head coach. It will be a little strange to face off against a team that I know so well, but at the same time for me that will make the occasion even more special."
The US matchday squad includes a total of eight new caps, six of which will be in the starting fifteen.
Led by 2007 Rugby World Cup prop Mike MacDonald, the hosts' pack has four players new to the Eagles squad, including a new hooker and tighthead prop in Chris Biller and Will Johnson respectively.
John Van Der Giessen will be joined by Hayden Smith in the second row, while Louis Stanfill will link up with flanker Peter Dahl and number 8 Nic Johnson in the back row.
In the back-line, the US has a little more experience, with Kevin Swiryn and Roland Suniula the only two uncapped players named in the backs division.
Mike Hercus will anchor things at out-half, while Mike Petri returns at scrum half to captain the side.
Junior Sifa, who plays his club rugby for Midleton in County Cork, Justin Boyd and Chris Wyles all return as well to give the back-line a threatening edge.
O'Sullivan added: "Despite the unavailability of a lot of our players, I believe we have still assembled a very competitive squad, with a good balance of youth and experience.
"The fact that we don't have quite a few of our usual players, allows me the opportunity to get a good look at the depth of our squad.
"With seven games ahead in as many weeks we will get to see everyone in our Eagles pool play and although the Ireland game is the start of this year's campaign, our ultimate goal comes at the end of the summer and will be qualifying for the Rugby World Cup.
"Ireland are coming off a Test against Canada, which gives them an advantage, but our players have to start somewhere and I'm confident they'll give it their all in this first Test of the season."
Amongst the players the US have unavailable for selection are last year's captain Todd Clever, the experienced trio of Paul Emerick, Kort Schubert and Salesi Sika and Biarritz flyer Taku Ngwenya.
Tickets for Sunday's game start at just $20 and are on sale here or you can call 1-800-225-2277.
USA TEAM & REPLACEMENTS (v Ireland, Setanta Challenge Cup, Sunday, May 31, Buck Shaw Stadium, Santa Clara, kick-off 1pm local time/9pm Irish time (live Setanta Sports Ireland)):
15 - Chris Wyles (Saracens FC)
14 - Kevin Swiryn (Old Puget Sound Beach RFC)*
13 - Junior Sifa (Midleton RFC)
16 - Joe Welch (Belmont Shore)
17 - Matekitonga Moeakiola (Park City Haggis)
18 - Courtney Mackay (Counties Manukau)
19 - JJ Gagiano (University of Cape Town)
20 - Tim Usasz (Nottingham RFC)*
21 - Ata Malifa (Belmont Shore RFC)*
22 - Alipate Tuilevuka (Provo Steelers)
* Denotes uncapped player