England wing Marland Yarde could miss the entire Six Nations as he requires surgery to repair a torn hip tendon.
The London Irish flyer suffered the injury in last weekend’s 20-11 Aviva Premiership defeat to Leicester and will now miss between 12 and 14 weeks, his club have confirmed.
Yarde featured in England's autumn international clash against Australia at Twickenham, after impressing on the summer tour to Argentina.
Yarde missed England's clashes against Argentina and New Zealand through injury but this fresh blow leaves a big hole to fill in both the Irish and England ranks.
England start their Six Nations campaign against France on February 1st, with Yarde now unlikely to be fit in time to make Stuart Lancaster's squad for that tournament opener.
London Irish have also confirmed hooker David Paice will miss eight to 10 weeks after fracturing his radius in that Leicester defeat last week.
Leicester's luckless back-five forward Tom Croft started England's wretched injury run this season.
The British and Irish Lion suffered knee ligament damage in September, and will miss the entire season - after missing most of the previous campaign with a serious neck injury.
Team-mate Manu Tuilagi will miss the entire Six Nations after surgery on a torn pectoral muscle earlier this month.
The wrecking-ball centre was primed for a comeback from the problem in September, only to suffer a serious complication at the last minute.
Another Tigers star, lock Geoff Parling, had surgery to repair a shoulder problem he picked up in England's loss to New Zealand that closed their autumn international run.
The former Newcastle Falcon will miss at least three months.
And Northampton Saints prop Alex Corbisiero is expected to be sidelined for three to four months after knee surgery, according to club boss Jim Mallinder.
Saracens centre Joel Tomkins is carrying a knee problem that is yet to be fully diagnosed, while Northampton full-back Ben Foden is in a similar predicament.
At least England boss Lancaster can breathe easy where Northampton skipper Dylan Hartley is concerned.
The Saints hooker has made a speedy recovery from the bruised lung he suffered against New Zealand, and will start for Northampton in their Aviva Premiership clash at Worcester Warriors on Saturday.
Saracens centre Brad Barritt’s ankle problem will keep him sidelined until the new year, but Lancaster will hope his chief defensive fulcrum will be fit for a Six Nations return.
And after hamstring trouble, Wasps' flyer Christian Wade is also fit again, starting Saturday's Premiership trip to London Irish.