O'Sullivan named his squad off the back of his first training camp with the domestic players last weekend.
The American squad for this match and the subsequent Test against Wales on June 6 includes a fairly even split of experience and youth in the forwards.
"It is great to be back coaching at international level again and I'm looking forward to the challenge immensely," O'Sullivan admitted.
"It is also 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."
Led by the USA's 2007 Rugby World Cup props Mike MacDonald and Mate Moeakiola, the forwards include six new players to the Eagles side.
2007 RWC players John Van der Giessen and Louis Stanfill also return to lead the locks and loose forwards, respectively.
Due to injury and unavailability, O'Sullivan has only been able to name one hooker and one scrum half in the panel.
The second hooker and scrum half will be named early next week after reviewing this weekend's Super League performances.
In the backs, the US has a little more experience with just four uncapped players and five players who played in the 2007 RWC.
Namely Mike Hercus, Mike Petri, Takudzwa Ngwenya, Chris Wyles and Salesi Sika all return to give the Eagles backs a threatening edge.
O'Sullivan added: "Despite the unavailability of 13 players, I believe we have still assembled a very competitive squad, with a good balance of youth and experience.
"With seven games ahead in as many weeks there is no doubt that the depth of our playing pool will be tested to the limit.
"Ireland is the first step on the road and judging by the energy and intensity displayed at our Denver training camp last weekend, the players are fired up for our first Test of the season."
The showdown between the USA and Ireland will begin at 1pm (local time/9pm (Irish time). Tickets start at just $10 and are currently on sale at www.tickets.com.
USA Rugby's CEO and President of Rugby Nigel Melville said: "One of our goals was to increase the number of international opponents in order to make our national teams more competitive.
"This schedule is a very good step forward in many respects. We are playing stiff competition against top international sides, which is really the only way to gauge our development.
"And with the increased amount of matches across the US, as well as the number of games being broadcast, this is a great opportunity for fans to get behind the Eagles and create some momentum."
Regionally, interest and participation in rugby has steadily increased in recent years, with more than 100 clubs located throughout California.
Patricia Ernstrom, executive director at the San Jose Sports Authority, said: "Our community is thrilled to welcome USA Rugby back to the Silicon Valley for this premier match against international powerhouses Ireland.
"Rugby fans are in for a wonderful afternoon of intense rugby, camaraderie, and fun and we are thankful for the tremendous support from our partners at Santa Clara University and the San Jose Earthquakes to host this great event.
"San Jose has an active sister city affiliation with Dublin, Ireland, and we are excited build on this international relationship and goodwill through sport."
Director of Setanta Sports, Robert Ryan, added: "Setanta Sports is very pleased to be supporting the third consecutive Setanta Challenge Cup, which for the first time brings national team opponents in the form of the USA and reigning Grand Slam champions Ireland. We look forward to a great match."
USA EAGLES Squad (v Ireland, Setanta Challenge Cup, Buck Shaw Stadium, Santa Clara, California, Sunday, May 31, kick-off 1pm local time/9pm Irish time):
Backs (13) - Justin Boyd (Dallas Harlequins RFC), Gavin DeBortolo (Eastern Suburbs Rugby), Taivalu Enosa (Tempe Rugby Football), Mike Hercus (Sunshine Coast Stingrays), Ata Malifa (Belmont Shore RFC), Takudzwa Ngwenya (Biarritz Olympique), Mike Petri (New York Athletic Club Rugby), Salesi Sika (Sporting Agen), Lotomau Junior Sifa (Midleton RFC), Roland Suniula (Pearl City Rugby), Kevin Swiryn (Old Puget Sound Beach RFC), Alipate Tuilevuka (Provo Steelers), Chris Wyles (Saracens FC).
Forwards (15) - Chris Biller (California), Peter Dahl (Belmont Shore RFC), Pat Danahy (Dublin University FC), JJ Gagiano (Univ. Cape Town), Nic Johnson (Denver Barbarians RFC), Will Johnson (Oxford University), Scott Lavalla (Dublin University FC), Mike MacDonald (Leeds Carnegie RFC), Courtney Mackay (Counties Manukau), Mate Moeakiola (Park City Haggis), Samu Manoa (San Francisco Golden Gate RFC), Shawn Pittman (Bayside RFC), Hayden Smith (Saracens FC), Louis Stanfill (New York Athletic Club Rugby), John Van Der Giessen (Denver Barbarians RFC).
Not considered due to injury: Matt Hawkins (Belmont Shore RFC), Valenese Malifa (Belmont Shore RFC), Alec Parker (Gentlemen of Aspen), Rikus Pretorius (Olympic Club Rugby)
Considered but unavailable: Todd Clever (Golden Lions), Paul Emerick (Overmach Parma), Troy Hall (Old Blue RFC), Brian Lemay (Boston Irish Wolfhounds RFC), Mike Palefau (Las Vegas RFC), Thretton Palamo (San Francisco Golden Gate RFC) Euan Sadden (Old Blue RFC), Kort Schubert (Olympic Club Rugby), Matt Wyatt (New York Athletic Club Rugby).