England flanker Tom Wood will miss England's opening two Six Nations matches, against Scotland and Italy, because of an injury to his big toe.
The 25-year-old, touted as a possible captain, will wear a protective boot for four weeks, ruling him out of the away matches on 4 and 11 February.
"There is never a good time to be injured and I'm obviously very disappointed," he said.
Chris Robshaw is favourite to lead the side at Murrayfield in his absence.
"An injury in one area is also an opportunity to develop strengths and improve in others," added Wood.
"I will still travel to Leeds next week so that I am part of the squad as it gels and begins to establish its own culture and values."
Harlequins' back row Robshaw was considered Wood's main rival for the captaincy in the wake of former skipper Lewis Moody's international retirement.
Wood's spell on the touchlines increases teh chances of Northampton team-mate Calum Clark or Scarlets' number eight Ben Morgan earning a debut in a new-look back row.
The injury will further limit interim head coach Stuart Lancaster's options for his first match in charge with fellow elite squad members Toby Flood,Courtney Lawes, Louis Deacon and Manu Tuilagi also ruled out.
Clark, Robshaw and Morgan, Leicester's versatile Tom Croft and Northampton's Phil Dowson, are the fit back-row players in Lancaster's 32-man group.
Wood made his England debut in last year's Six Nations opener and was one of the stars of a hard-fought victory against Wales at the Millennium Stadium.
He appeared in each of England's subsequent matches en route to the championship, but Croft was preferred for much of the team's World Cup campaign in New Zealand
Temporary injury cover could be called up from the second-string Saxons squad with Saracens' open-side flanker Andy Saull and Sale's James Gaskell among the possible candidates for promotion.