Team manager Martin Johnson has lost the services of an almost endless list of possible starters, with six recent Lions tourists among the most talked-about absentees.
England will be without 2009 Lions Andrew Sheridan, Lee Mears, Phil Vickery Harry Ellis, Riki Flutey and Simon Shaw for the games against Australia, Argentina and New Zealand.
Their enforced absence leaves Johnson with just four players who toured South Africa with the Lions in his latest squad, with forwards Tom Croft, Tim Payne and Joe Worsley joined by wing Ugo Monye in his much-changed 32-man party.
England have also lost the likes of Delon Armitage, Nick Easter, Toby Flood, Olly Morgan and Tom Rees, while injury also prevented Saxons squad member Danny Cipriani from pushing for a senior recall.
Julian White, a Test Lion against the All Blacks four years ago, was one of the latest to miss out through an injury he picked up last weekend after he had been touted for an international recall.
There is a still a large Lions contingent among Johnson's chosen squad, however, albeit from that 2005 tour rather than 2009 equivalent.
World Cup winning hooker Steve Thompson is included, as are fellow 2005 Lions Ben Kay, Lewis Moody and Jonny Wilkinson.
There are high-profile call ups for uncapped youngsters Courtney Lawes and Richard Blaze, as well as veteran Bath props David Barnes and Duncan Bell.
James Haskell returns to the first-team squad after his move to France, while Sale scrum-half Richard Wigglesworth, Brive fly-half Andy Goode and Harlequins wing David Strettle are given another chance to impress.
"We've had to make a number of changes to the senior squad because of injuries but we have strength in depth," said former Lions skipper Johnson.
"The whole squad is looking forward to three very tough games in November…and each of the players coming in has the opportunity to push themselves into contention for the first match against Australia."
Revised England EPS squad
Forwards: Steffon Armitage (London Irish), David Barnes (Bath Rugby), Duncan Bell (Bath Rugby), Richard Blaze (Leicester Tigers), Steve Borthwick (Saracens, captain), George Chuter (Leicester Tigers), Jordan Crane (Leicester Tigers), Tom Croft (Leicester Tigers), Louis Deacon (Leicester Tigers), Dylan Hartley (Northampton Saints), James Haskell (Stade Francais), Ben Kay (Leicester Tigers), Courtney Lawes (Northampton Saints), Lewis Moody (Leicester Tigers), Tim Payne (London Wasps), Steve Thompson (CA Brive), David Wilson (Bath Rugby), Joe Worsley (London Wasps)
Backs: Matt Banahan (Bath Rugby), Danny Care (Harlequins), Mark Cueto (Sale Sharks), Ben Foden (Northampton Saints), Shane Geraghty (Northampton Saints), Andy Goode (CA Brive), Dan Hipkiss (Leicester Tigers), Paul Hodgson (London Irish), Ugo Monye (Harlequins), David Strettle (Harlequins), Mathew Tait (Sale Sharks), Mike Tindall (Gloucester Rugby), Richard Wigglesworth (Sale Sharks), Jonny Wilkinson (Toulon)
NB Bold denotes Lions tourist