There will not be a single member of Saints’ Aviva Premiership table-topping side in England’s starting 15 to face Uruguay on Saturday.
Tom Wood, who had started in the games against Fiji, Wales and Australia, is left on the bench, while Courtney Lawes remains out with a knee injury.
Kieran Brookes, who joined Saints from Newcastle Falcons during the summer, is another who misses out on a place in the matchday squad.
The game at Manchester City’s Etihad Stadium will be a dead rubber after defeats to Wales and Australia at Twickenham saw England eliminated from the World Cup.
Consequently, head coach Stuart Lancaster has opted to shake things up, making nine changes to the team that lost 33-13 to the Wallabies last Saturday.
Henry Slade and Jack Nowell will make their World Cup debuts and they will be joined by scrum-half Danny Care and full-back Alex Goode, who are also making their RWC bows.
In the pack, Mako Vunipola starts in place of Joe Marler, while James Haskell and Nick Easter replace Wood and Ben Morgan respectively.
Lancaster said: “Brad Barritt and Courtney Lawes are not available this weekend and Ben Morgan and Ben Youngs will not be able to train fully until Thursday.
“This is an opportunity for us to finish the tournament with a strong performance against Uruguay and a chance for the likes of young players such as Jack Nowell and Henry Slade to play in a World Cup.
“We owe it to ourselves and the supporters who have been brilliant throughout.
“This is an important game for rugby in the north of England and we want to give those people who have been looking forward to this game something to cheer about.”
England (v Uruguay, City of Manchester Stadium, 8pm, BST, Saturday, October 10, 2015)
15 Alex Goode (Saracens, 18 caps)
14 Anthony Watson (Bath Rugby, 14 caps)
13 Henry Slade (Exeter Chiefs, 1 cap)
12 Owen Farrell (Saracens, 34 caps)
11 Jack Nowell (Exeter Chiefs, 9 caps)
10 George Ford (Bath Rugby, 16 caps)
9 Danny Care (Harlequins, 52 caps)
1 Mako Vunipola (Saracens, 26 caps)
2 Tom Youngs (Leicester Tigers, 27 caps)
3 Dan Cole (Leicester Tigers, 55 caps)
4 Joe Launchbury (Wasps, 27 caps)
5 Geoff Parling (Exeter Chiefs, 28 caps)
6 James Haskell (Wasps, 61 caps)
7 Chris Robshaw (capt, Harlequins, 42 caps)
8 Nick Easter (Harlequins, 53 caps)
16 Jamie George (Saracens, 2 caps)
17 Joe Marler (Harlequins, 36 caps)
18 David Wilson (Bath Rugby, 43 caps )
19 George Kruis (Saracens, 9 caps)
20 Tom Wood (Saints, 41 caps)
21 Richard Wigglesworth (Saracens, 26 caps)
22 Jonathan Joseph (Bath Rugby, 15 caps)
23 Mike Brown (Harlequins, 42 caps)