Leo Cullen also returns after missing out on selection for the Rugby World Cup, as does his Leinster teammates Jamie Heaslip and Bernard Jackman.
Munster lock Paul O'Connell has been left out having failed to recover from the back injury sustained during the World Cup and could miss the entire tournament if he requires surgery.
The backrow continues to be one of the most competitive areas with Johnny O'Connor included in a RBS 6 Nations squad for the first time since 2006 and secondrow Mick O'Driscoll also returns.
In addition to the uncapped outhalf Sexton as one of the 15 backs named in the squad, Robert Kearney, Luke Fitzgerald and Tommy Bowe are all added to the back division for the tournament.
O'Sullivan said: "First and foremost I feel this squad reflects the form of the players in the Heineken Cup and Magners League and I am 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 backrow, 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".
"The RBS 6 Nations represents a great opportunity for the squad to get back to the standards we have achieved in the past.
"It is the tournament that we always want to do well in and this year's championship is really open with no clear favourites, so it really is a case of only looking forward to your next game, which starts with an Italy side who always begin the tournament well."
Neil Best (Belfast Harlequins/Ulster)
Rory Best (Belfast Harlequins/Ulster)
Tony Buckley (Shannon/Munster)
Leo Cullen (Blackrock College/Leinster)
Simon Easterby (Llanelli)
Jerry Flannery (Shannon/Munster)
John Hayes (Bruff/Munster)
Cian Healy (Clontarf/Leinster)
Jamie Heaslip (Clontarf/Leinster)
Marcus Horan (Shannon/Munster)
Bernard Jackman (Clontarf/Leinster)
Denis Leamy (Cork Constitution/Munster)
Donncha O'Callaghan (Cork Constitution/Munster)
Johnny O'Connor (Galwegians/Connacht)
Mick O'Driscoll (Cork Constitution/Munster)
Malcolm O'Kelly (St.Mary's College/Leinster)
Alan Quinlan (Shannon/Munster)
David Wallace (Garryowen/Munster)
Tommy Bowe (Belfast Harlequins/Ulster)
Girvan Dempsey (Terenure College/Leinster)
Gordon D'Arcy (Lansdowne/Leinster)
Gavin Duffy (Galwegians/Connacht)
Luke Fitzgerald (Blackrock College/Leinster)
Shane Horgan (Boyne/Leinster)
Robert Kearney (UCD/Leinster)
Geordan Murphy (Leicester)
Brian O'Driscoll (UCD/Leinster)
Ronan O'Gara (Cork Constitution/Munster)
Eoin Reddan (Wasps)
Jonathan Sexton (St.Mary's College/Leinster)
Peter Stringer (Shannon/Munster)
Andrew Trimble (Ballymena/Ulster)
Paddy Wallace (Ballymena/Ulster)
Not considered due to injury:
Simon Best (Belfast Harlequins)
Stephen Ferris (Dungannon/Ulster)
Paul O'Connell (Young Munster/Munster)