England trio Alex Corbisiero, Marland Yarde and Christian Wade will miss this Saturday's QBE international against New Zealand, coach Stuart Lancaster has announced.
Corbisiero misses out because of a recurring knee problem, while Yarde and Wade fall short in their battle to return to fitness.
"Alex took part in Tuesday morning's forwards training session but suffered some discomfort to his knee," England head coach Lancaster said.
"He did not train on Tuesday afternoon and will not be available for selection for the weekend."
Corbisiero's joins Mako Vunipola in being absent at the loosehead prop position, and Lancaster said that it gave Joe Marler and Matt Mullan the opportunity to shine.
"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," he added.
New Zealand head into the match at Twickenham looking to avenge the 38-21 loss last December - their only defeat since August 2011.