England's injury problems continued to mount after wing Christian Wade was ruled out for up to six months with damaged foot ligaments.
Wade will undergo surgery after being hurt in Wasps' 19-12 Aviva Premiership victory over London Irish on Saturday and will miss the entire RBS 6 Nations.
"It's devastating news for both the player and the club," Wasps director of rugby Dai Young said.
Wade was due to win his second cap in last month's QBE Internationals, only for a hamstring injury to prevent him from starting against Argentina and New Zealand.
Head coach Stuart Lancaster was keen to give the British and Irish Lion a more prominent role amid the ongoing deterioration of Chris Ashton's form and he was set to start the Six Nations opener against France on February 1.
But, unless he heals quicker than expected, he will not play again for Wasps this season and his participation in the summer tour to New Zealand is in grave doubt.
"Christian was hugely unlucky to miss out on being capped this autumn and he had hoped to push on and put in some good performances for Wasps to get him in contention for Six Nations selection," Young said.
"It is a huge blow for him but he is a young player with a huge future and his time will come around again."
England's options out wide are depleting rapidly with Marland Yarde and Ben Foden set to miss the Six Nations with respective hip and knee injuries.
Wade's absence is likely to result in a Test reprieve for Ashton despite struggling throughout the autumn, while Charlie Sharples, David Strettle, Jonny May and Ugo Monye are in contention for promotion from the Saxons.
The depth of England's squad will be tested in the Six Nations as they contend with a disturbing succession of injuries.
Flanker Tom Croft and prop Alex Corbisiero have been ruled out of the Championship altogether, while centre Manu Tuilagi and lock Geoff Parling are unlikely to be involved.
Centre Joel Tomkins is another three-month casualty due to a knee injury, but his poor performances against Australia, Argentina and New Zealand last month put his participation in serious doubt.
Brad Barritt should be back from foot surgery by Christmas to reinforce the midfield.
Meanwhile, England have announced that next summer's Test series against New Zealand will be played in Auckland, Dunedin and Hamilton.
The series opens at Eden Park on June 7, continues at Forsyth Barr Stadium seven days later and concludes at Waikato Stadium on June 21.
One midweek match has been scheduled against seven-times Super Rugby champions the Crusaders in Christchurch on June 17.
Lancaster views the itinerary as the ideal opportunity to narrow the gap on the All Blacks, who triumphed 30-22 in an enthralling contest at Twickenham last month.
"To play the world champions in their own back yard is the ultimate test," Lancaster said.
"We saw in the Rugby Championship and the QBE Internationals what a formidable team and rugby nation New Zealand is.
"This is our final tour before the World Cup and is massively important for us to benchmark ourselves against the number one team in the world.
"Playing three Tests and a midweek match will give us the opportunity to take 35 to 40 players who will get a chance to lay down a marker 15 months out from the World Cup."