Gloucester winger James Simpson-Daniel has been ruled out of England's autumn Tests after injuring his ankle.
The 26-year-old requires surgery on damaged ankle ligaments and will be sidelined for three months.
His Gloucester team-mate Luke Narraway is also doubtful for England's first game against the Pacific Islands on 8 November because of a hamstring injury.
England team manager Martin Johnson is expected to name a replacement for Simpson-Daniel on Friday.
Both Simpson-Daniel and Narraway were injured during Gloucester's Heineken Cup defeat by Cardiff Blues at the Millennium Stadium on Sunday.
"To lose a player of James's quality is obviously a massive blow to us"
"On behalf of the squad my thoughts are with James," said Johnson.
"The coaching and medical teams from Gloucester and England will be in regular contact with him during his recovery and rehabilitation."
The injury is a cruel blow to Simpson-Daniel, who has been in decent form this season and was the Guinness Premiership player of the season last year.
Despite his talent, Simpson-Daniel has been restricted to only 10 England caps following a catalogues of injuries and illness.
Gloucester's head coach Dean Ryan said: "To lose a player of James's quality is obviously a massive blow to us.
"He is an outstanding player and central to our attacking threat. Considering the other injuries we have across our backline this could not have come at a worse time for us."
England are also monitoring the fitness of Sale full-back Mathew Tait, who has suffered a hamstring injury.
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Harlequins winger David Strettle may have been next in line to replace Simpson-Daniel but he is recovering from a broken metatarsal.
Johnson's other wing options in the second-string England Saxons are Topsy Ojo, who made his Test debut in New Zealand during the summer, Ugo Monye and Matt Banahan.
But England may turn to Simpson-Daniel's Gloucester team-mate Olly Morgan, who could be fast-tracked from outside the England fold into the senior squad.
Earlier this week, Johnson replaced injured duo Lewis Moody and Jonny Wilkinson in the elite squad with Michael Lipman and Danny Cipriani.
Bath's Nick Abendanon was also drafted into the squad in place of Tom Varndell, who is short of match practice after falling out of favour at Leicester.
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