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Back rower Mike Williams, prop Nathan Catt and versatile back Alex Lozowski are the uncapped trio, while prop Ellis Genge, 21, is also in the 34-man squad.
Flanker James Haskell, lock Maro Itoje, winger Anthony Watson, back rower Jack Clifford and winger Jack Nowell all return for the champions after injury.
"We are looking forward to being daring in our [first] game against France on 4 February," said head coach Eddie Jones.
England are without a number of players through injury, including both Mako and Billy Vunipola and former captain Chris Robshaw.
Of those players in the squad, the likes of Haskell, Anthony Watson, Joe Launchbury and George Kruis have either just returned from injuries or are still fighting their way back to full fitness.
The experienced Tom Wood retains his place after a fine November series, while lock Charlie Ewels, prop Kyle Sinckler and hooker Tommy Taylor have just a handful of caps between them.
England go into the tournament as defending champions having won the Grand Slam in 2016, and on the back of a 14-game winning streak, equalling the record set by Sir Clive Woodward's side in the build-up to the 2003 World Cup.
"This time last year I said the long-term strategy for England is to develop a side who can be the most dominant team in world rugby," added Jones.
"Obviously I've been pleased with how the team's progressing, but there's still plenty to improve on.
"At the start of last year's Six Nations I probably didn't realise the enormity of the tournament and how intense the rivalry is between the countries, so this year we'll be better prepared for it."
Jones said Catt, Williams and Lozowski are "all guys who have great physical capabilities", adding: "With a number of injuries to some key players it's a great opportunity for them."
And he praised his returning big names who missed the autumn Tests because of injury, saying he was "looking forward to those guys coming in and challenging for a spot and adding strength".
He continued: "Maro Itoje has done well for his club [Saracens] as has Jack Nowell [Exeter]. James Haskell was magnificent for England last year and is a fierce player. Anthony Watson has been a fine player for England and is one the most prolific try scorers for the number of Tests he has played."
Jones has also added visual awareness coach Dr Sherylle Calder to his coaching team.
Calder, part of Woodward's back-up staff, will work with the team on a consultancy basis.
BBC Radio 5 live rugby union reporter Chris Jones
After constantly throwing selectorial curve balls over the past year, this is by far Eddie Jones' most predictable squad yet.
With Mako Vunipola ruled out and Joe Marler struggling, Jones has named four loose-head props, including uncapped Nathan Catt and Leicester tyro Ellis Genge.
And while there are injury absentees - notably the Vunipolas and Chris Robshaw - key players such as Maro Itoje and Jack Nowell return.
England squad for 2017 Six Nations
Forwards:
Nathan Catt (Bath Rugby), Jack Clifford (Harlequins), Dan Cole (Leicester Tigers), Charlie Ewels (Bath Rugby), Ellis Genge (Leicester Tigers), Jamie George (Saracens), Teimana Harrison (Northampton Saints), Dylan Hartley (Northampton Saints), James Haskell (Wasps), Nathan Hughes (Wasps), Maro Itoje (Saracens), George Kruis (Saracens), Joe Launchbury (Wasps), Courtney Lawes (Northampton Saints), Joe Marler (Harlequins), Matt Mullan (Wasps), Kyle Sinckler (Harlequins), Tommy Taylor (Wasps), Mike Williams (Leicester Tigers), Tom Wood (Northampton Saints)
Backs:
Mike Brown (Harlequins), Danny Care (Harlequins), Elliot Daly (Wasps), Owen Farrell (Saracens), George Ford (Bath Rugby), Jonathan Joseph (Bath Rugby), Alex Lozowski (Saracens), Jonny May (Gloucester Rugby), Jack Nowell (Exeter Chiefs), Henry Slade (Exeter Chiefs), Ben Te'o (Worcester Warriors), Anthony Watson (Bath Rugby), Marland Yarde (Harlequins), Ben Youngs (Leicester Tigers)
England have named three uncapped players in their Six Nations squad.