England flanker Joe Worsley has been ruled out of the opening two games of the Six Nations after failing to recover from a neck injury.
Wasps say Worsley will return to contact training next week
The Wasps back-rower has not played for his club since 5 January and will miss the clash with Wales on 2 February and the match against Italy a week later.
Winger Paul Sackey will join up with the squad on Sunday subject to being symptom-free after contracting mumps.
And flanker Lewis Moody (groin) is back in the Leicester side this weekend.
Tongan wing Lesley Vainikolo, who grabbed the headlines when he was named in England's Six Nations squad, has been left out of the Gloucester side that will face Wasps because of a knee injury.
However, Gloucester coach Dean Ryan says the injury is not a long-term issue and insists Vainikolo will join up with the England squad when they convene in Bath on Sunday night.
Moody has been a concern for the England management after featuring in just one of Leicester's last five games but will play against Newcastle on Saturday.
His selection for the Tigers will be a major boost for England coach Brian Ashton after the injuries to Worsley as well as Harlequins number eight Nick Easter.
Easter last played for Quins on 29 December, missing the last three games, and was due to play this week in the Premiership match against Sale.
However, he tweaked his knee in training and has been rested as a precaution.
The back-row concerns are a further worry for Ashton as he begins his preparations for the Wales game.
London Irish scrum-half Peter Richards was ruled out of the competition on Wednesday, Wasps lock Simon Shaw will miss the start of it while wing Sackey caught mumps last week.
STARTING ENGLISH PLAYERS THIS WEEKEND
Sale: Mark Cueto, Charlie Hodgson, Richard Wigglesworth, Andrew Sheridan
Harlequins: David Strettle
Leicester: George Chuter, Lewis Moody, Ben Kay, Louis Deacon
Newcastle: Mathew Tait, Jonny Wilkinson, Toby Flood, Jamie Noon
Gloucester: Iain Balshaw, Mike Tindall, Luke Narraway
Wasps: Danny Cipriani, Phil Vickery, James Haskell, Tim Payne, Tom Rees
Bristol: Mark Regan
Bath: Michael Lipman, Steve Borthwick, Matt Stevens, Lee Mears
London Irish: Paul Hodgson
The 28-year-old was placed into quarantine, forcing him to miss Wasps' Heineken Cup clash with Munster on Saturday, and a saliva test on Monday confirmed the diagnosis.
Wasps believe Sackey "should cease to be contagious within the week" and "should be able to return to training one or two days after his symptoms subside".
To prevent the virus spreading, the club are immunised their squad with the MMR vaccine while Gloucester did the same.
Richards suffered a biceps injury playing for his club London Irish in the Heineken Cup last weekend and is not expected to return to action for three months.
Andy Gomarsall of Harlequins and Sale's Richard Wigglesworth will now fight it out for the scrum-half jersey.
Exiles number nine Paul Hodgson, Bath flanker Michael Lipman and Gloucester number eight Luke Narraway were called up as cover last week and will return to the 33-man training squad on Sunday.
Shaw was stretchered off early in the second half of the Munster game with soft tissue damage to his ankle after falling awkwardly beneath a pile of bodies.
Wasps say the 34-year-old is walking without the assistance of crutches and is recovering "remarkably well", but he is still likely to miss the first two matches.
Ashton says he will be keeping "everything crossed" this weekend
Leicester scrum-half Harry Ellis, Bristol number nine Shaun Perry and Bristol number eight Dan Ward-Smith are also injured.
Speaking at the official launch of the Six Nations earlier this week, Ashton told BBC Sport that he will not ask for players to miss this weekend's Premiership games despite the risk of further injuries.
While 27 of Ashton's training squad are starting for their clubs in a full weekend of Premiership fixtures, the Magners League, which features teams from Wales, Scotland and Ireland, has a rest until the 29 February.
The situation evokes memories of last year when England brought forward the naming of their team to face Ireland in the hope that Premiership clubs would rest their players.
A new deal between the Rugby Football Union and the clubs, which will see England players released 13 or 14 days before Tests, does not come into effect until the summer.
"I wouldn't make requests for players to be rested," he said. "Having worked in the Premiership I know exactly what the situations are. They will do what they think is best.
At international level there is no substitute for experienced players when the going gets tough
England coach Brian Ashton
"There is an argument to say that having a tough game before an international is not a bad thing. For some players, having a week off is maybe not the best preparation."
Meanwhile Ashton, who led England to the World Cup final last October after being in the job for less than a year, has said he is determined to see his side become more expansive during the Six Nations.
England came under fire for their approach in France but Ashton said: "We played rugby to suit a purpose in the World Cup, we know we have to move our game on. Once you stand still in this game, people overtake you.
"I am not setting any deadlines on it. I have challenged the players and I have challenged the coaching staff, and that includes myself, to get some add-on value from where we were in the World Cup.
"If that doesn't happen in the first game and we win, I'll still be happy.
"We have to start with a good performance against Wales. We have some continuity and we have a platform to play from."