Flood's French move ends England career
England's rugby player Toby Flood (C) passes the ball during the captain's run at Twickenham Stadium, southwest of London, on November 1, 2013
Leicester fly-half Flood, a veteran of 60 Tests, is set to join French giants Toulouse at the end of this season.
That has led Lancaster, holding to his line not to select overseas-based players, to bring in uncapped Bath stand-off George Ford in addition to current first-choice No.10 Owen Farrell ahead of the 2015 World Cup in England.
"I have met Toby Flood several times and told him I really wanted him to stay at Leicester and play for England," said Lancaster in a Rugby Football Union (RFU) statement.
"He has made a lifestyle choice and we respect that but given the RFU's policy of not selecting players based overseas save for exceptional circumstances it was important that we allow others such as George Ford to progress."
"I am delighted for George who is rewarded for his form for Bath."
Injuries mean England are without centre Manu Tuilagi (chest), back-row Tom Croft (knee), wing Marland Yarde (hip), prop Alex Corbisiero (knee), wing Christian Wade (foot), lock Geoff Parling (shoulder), prop David Wilson (calf) and full-back Ben Foden (knee).
Their places have been taken by Luther Burrell (Northampton), Tom Johnson (Exeter), Jonny May (Gloucester), Matt Mullan (Wasps), Jack Nowell (Exeter), Ed Slater (Leicester), Henry Thomas (Sale) and Anthony Watson (Bath) respectively.
However, Lancaster said he was optimistic some of those currently sidelined would return in time for the post-season three-Test series away to world champions New Zealand.
"We are hopeful that some of those injured may be available before the end of the Six Nations and certainly for the (summer) New Zealand tour," he said.
England won four of their five matches in last season's Six Nations but finished runners-up to Wales on points difference after suffering a 30-3 thrashing by the eventual champions in a title-decider at Cardiff's Millennium Stadium.
England were the only European side to beat one of the southern 'big three' of Australia, New Zealand and South Africa during the 2013 end of year Tests when they defeated the Wallabies 20-13 at Twickenham in November.
Their forwards were impressive during a 30-22 loss to New Zealand later that month.
But a lack of cutting edge behind the scrum against the All Blacks raised questions about the absence of an obvious 'playmaker' in the back division -- something many observers believe is a necessary requirement if England are to add a second World Cup title next year in addition to their 2003 triumph.
Hopes are high the 20-year-old Ford, coached by his father, Mike, the former England defence chief, could be that player although, given Farrell is the Test side's first-choice goalkicker, the rising star is likely to be on the bench initially.
England's first match of the 2014 Six Nations is against France in Paris on February 1.
Chris Ashton (Saracens), Brad Barritt (Saracens), Mike Brown (Harlequins), Luther Burrell (Northampton)Danny Care (Harlequins), Lee Dickson (Northampton), Kyle Eastmond (Bath), Owen Farrell (Saracens), George Ford (Bath), Alex Goode (Saracens), Jonny May (Gloucester), Stephen Myler (Northampton), Jack Nowell (Exeter), Billy Twelvetrees (Gloucester), Ben Youngs (Leicester), Anthony Watson (Bath), Richard Wigglesworth (Saracens)
David Attwood (Bath), Dan Cole (Leicester), Dylan Hartley (Northampton), Matt Kvesic (Gloucester), Tom Johnson (Exeter), Joe Launchbury (Wasps), Courtney Lawes (Northampton), Joe Marler (Harlequins), Ben Morgan (Gloucester), Matt Mullan (Wasps), Chris Robshaw (Harlequins), Ed Slater (Leicester), Henry Thomas (Sale), Billy Vunipola (Saracens), Mako Vunipola (Saracens), Rob Webber (Bath), Tom Wood (Northampton), Tom Youngs (Leicester)
England 2014 Six Nations Fixtures:
Feb 01: v France (a)
Feb 08: v Scotland (a)
Feb 22: v Ireland (h)
Mar 09: v Wales (h)
Mar 15: v Italy (a)