Sale scrum-half Richard Wigglesworth will make his first England start in Saturday's RBS Six Nations clash against France in Paris on Saturday.
Wigglesworth came on during the last match against Italy
Wigglesworth wins his second cap after replacing Andy Gomarsall, who drops out of the match-day 22 altogether.
Skipper Phil Vickery and fellow prop Andrew Sheridan return to the front row after missing the win in Italy.
The uncapped London Irish scrum-half Paul Hodgson and Leicester flanker Tom Croft are among the replacements.
Both will be making their England debuts should they come off the bench at the Stade de France.
Prop Tim Payne and Matt Stevens are the other players who started against Italy that miss out, although Stevens will travel to Paris as a replacement.
Coach Brian Ashton has resisted the temptation to make wholesale changes despite the stuttering performance in Rome last time out.
I felt we needed a change to get some energy and tempo into into our game
Brian Ashton on Gomarsall's demotion
With Sheridan and Vickery returning after injury and illness respectively, the only major casualty is Gomarsall.
A key performer in England's surprise run to the World Cup final, the 33-year-old has been axed after two less-than-convincing displays against Wales and Italy, casting doubt on his long-term international future.
"Andy has not reached the level he played at during the World Cup," Ashton told BBC Radio 5 Live.
"I was hoping the stimulus of international rugby would help him get back to where he was then, but he hasn't quite made it unfortunately.
"I felt we needed a change to get some energy and tempo injected into our game. Hopefully Richard Wigglesworth and Paul Hodgson, who is an incredibly enthusiastic young man, can both do that."
Blackpool-born Wigglesworth was a member of England's under-21 Grand Slam-winning side in 2004 and also helped England Saxons land the Churchill Cup last summer.
The 24-year-old, who has also turned out at fly-half on occasion for Sale, has made 13 starts in the Sharks' 21 games so far this season, and made his England debut as a second-half replacement in Rome.
"I thought when he came on against Italy he was very composed in what could have been a tricky situation, and I am looking forward to him building on that," Ashton added.
Vickery pulled out of the Italy match on the day of the game with a stomach bug but proved his fitness by playing almost the entire game for Wasps in their win at Bath last Saturday.
It is a big game for some players this week, there is no doubt about it
Sheridan was hospitalised before the Italy game with an infected cut on his heel.
Locks Steve Borthwick (knee) and Simon Shaw (ankle), centre Jamie Noon (hamstring), wing Paul Sackey (thumb) were all injury worries but have been deemed fit enough to play.
Ashton admits there could be more changes if certain players do not produce what he expects of them in Paris.
"It is a big game for some players this week, there is no doubt about it," he added.
"I put a lot of faith in players because we wanted some continuity and stability, and the World Cup was the platform to build on," he added.
"We have seen some signs of that, but not the signs I was looking for. The players are well aware this is a big game for them this weekend."
England team: Balshaw (Gloucester); Sackey (Wasps), Noon (Newcastle), Flood (Newcastle), Vainikolo (Gloucester); Wilkinson (Newcastle), Wigglesworth (Sale); Sheridan (Sale Sharks), Regan (Bristol), Vickery (Wasps, capt), Shaw (Wasps), Borthwick (Bath), Haskell (Wasps), Lipman (Bath), Easter (Harlequins).
Replacements: Mears (Bath), Stevens (Bath), Kay (Leicester), Croft (Leicester), Hodgson (London Irish), Cipriani (Wasps), Tait (Newcastle).