Chris Robshaw is to have surgery on his injured shoulder and will play no part in England's Six Nations campaign.
The flanker damaged his left shoulder during Harlequins' New Year's Day game against Worcester and consulted a specialist on Monday.
An immediate operation has been booked in, and Quins estimate their forward will miss around 12 weeks.
That timescale leaves Robshaw no chance of featuring in England's Grand Slam defence as Eddie Jones' injury problems intensify ahead of the January 20 squad announcement.
Billy Vunipola has been ruled out while brother Mako could also be missing, and there are further concerns about James Haskell and Joe Marler.
Dylan Hartley's latest suspension, meanwhile, means his captaincy is in question until he proves he is fit enough to play.
England begin the Six Nations at home to France on February 4 and finish up in Dublin on March 18.