The uncapped Leinster duo have been rewarded for their fine form this season, but both are rookies - even at provincial level.
Healy, 20, has made just eight senior appearances for Leinster while 22-year-old fly-half Sexton has also impressed and will compete with Paddy Wallace to become Ronan O'Gara's understudy.
Wingers Rob Kearney, Luke Fitzgerald and Tommy Bowe and number eight Jamie Heaslip further reduce the average age of the squad.
"First and foremost I feel this squad reflects the form of the players in the Heineken Cup and Magners League," said O'Sullivan
"I'm excited to introduce some young blood into the mix for the Six Nations.
"Some of the younger players have really put their hands up through their performances and have earned their spot in the squad.
"At the same time it again threw up some tight calls, especially in the back row, which always seems to be the same every time we select a squad.
"However, I think we have the balance right going into the championship."
O'Sullivan has refused to confine his attention to the youth ranks in searching for new additions to the squad, however, with hooker Bernard Jackman and locks Mick O'Driscoll and Leo Cullen far more seasoned campaigners.
Johnny O'Connor, who won the last of his 12 caps against England in 2006, has played his way into the reckoning for the number seven jersey with a string of standout displays for Connacht.
Competition for back row places is fierce and Leinster openside Keith Gleeson was unfortunate not to be included, losing out to the younger O'Connor.
In all, there are 22 survivors from the original squad that performed so abysmally at the World Cup
Isaac Boss has paid the price for his slump in form by being axed with Peter Stringer and Eoin Reddan the only scrum-halves selected in the 33.
Brian Young, Brian Carney and Frankie Sheahan have also been dropped, while Denis Hickie retired after the tournament in France.
Munster prop Tony Buckley, a late call-up when Simon Best was struck down by illness at the World Cup, replaces the Ulster front row for the Six Nations.
O'Connell, Best and Stephen Ferris have not been considered due to injury.
O'Connell has been sidelined with a back problem sustained during the World Cup and is almost certain to miss the opening two Six Nations games against Italy and France.