England have been struck by a trio of injury-enforced withdrawals for Saturday's QBE International against New Zealand headed by confirmation that Alex Corbisiero has been ruled out.
The injury crisis at loosehead prop has deepened with Corbisiero joining Mako Vunipola on the list of absentees, while wings Marland Yarde and Christian Wade have conceded defeat in their fitness battles.
It is the loss of Corbisiero, a star of the British and Irish Lions' tour to Australia, to a recurring knee problem that will be felt most acutely and England will be hoping desperately that Joe Marler is given the green light to face the All Blacks.
Marler, the last remaining senior loosehead in the squad, was concussed in Saturday's 31-12 victory over Argentina and is following graduated return-to-play protocols.
The Harlequins front row is on course to recover but should he suffer a setback, England will be down to their fourth choice in the position - Wasps rookie Matt Mullan, who at the very least will be named on the bench.
Corbisiero missed the autumn opener against Australia and his latest comeback from knee trouble lasted for only the second half against Argentina.
"Alex took part in Tuesday morning's forwards training session but suffered some discomfort to his knee," England head coach Stuart Lancaster said.
"He did not train on Tuesday afternoon and will not be available for selection for the weekend.
"It's disappointing for Alex having missed last year's Six Nations because of an injury to his other knee.
"With Mako also unavailable, it's a great opportunity for Joe Marler and Matt Mullan, who has been with us all week and is raring to go in the 23."
Marler has undergone a daily increase in activity as demanded by concussion guidelines and is due to undergo a full contact session on Thursday, the day Lancaster names his team.
"Joe Marler has had no symptoms of concussion since Saturday," England team doctor Phil Batty said.
"He has passed all his cognitive function (CogSport) tests and balance assessments and completed a skills session on Tuesday without any problems."
Hopes that Yarde would recover from his hip problem ended on Tuesday afternoon, when it was also confirmed that Wade's tight hamstring would end his involvement.
Their absence means the struggling Chris Ashton has won a reprieve on the right wing, continuing in what will be an unchanged backline.
"Marland Yarde and Christian Wade have not recovered in time to be available for this game," Lancaster said.
"We've had a good start to the week and now it's a case of tapering down the training and getting ourselves ready for the ultimate challenge.
"The Twickenham crowd has been great over the last two weeks and we know they will be just as vocal as they were against New Zealand last year."
Lancaster trimmed his squad to 23 players on Tuesday night with tighthead prop, where Dan Cole and David Wilson are competing, the only likely change to the starting XV.
England 23-man squad v New Zealand: Forwards: D Cole (Leicester Tigers), D Hartley (Northampton Saints), J Launchbury (London Wasps), C Lawes (Northampton Saints), J Marler (Harlequins), B Morgan (Gloucester Rugby), M Mullan (London Wasps), G Parling (Leicester Tigers), C Robshaw (Harlequins), B Vunipola(Saracens), D Wilson (Bath Rugby), T Wood (Northampton Saints), T Youngs (Leicester Tigers). Backs: C Ashton (Saracens), M Brown (Harlequins), L Dickson (Northampton Saints), O Farrell (Saracens), T Flood (Leicester Tigers), B Foden (Northampton Saints), A Goode (Saracens), J Tomkins (Saracens), B Twelvetrees (Gloucester Rugby), B Youngs (Leicester Tigers).