Jason Robinson and Neil Back have become the latest victims of England's RBS 6 Nations injury problems.
Both players went off during the 26-9 victory over Wales in Cardiff and could struggle to make England's March 9 appointment with Italy at Twickenham.
Full-back Robinson suffered a twisted knee, while flanker Back hurt his calf - giving England boss Clive Woodward further fitness worries during a campaign already riddled by injuries.
Props Jason Leonard (hamstring), Julian White (knee) and Phil Vickery (back) are all unlikely to feature in the remaining games against Italy, Scotland and Ireland.
But fly-half Jonny Wilkinson and wing Dan Luger, who also departed the Millennium Stadium action early, should be fit for Italy.
"Jason Robinson and Neil Back are concerns," admitted Woodward, whose lengthy casualty list additionally includes the likes of Matt Dawson, Austin Healey and Iain Balshaw.
Wasps back Josh Lewsey and Leicester's Tim Stimpson will come into contention for the number 15 jersey should Robinson be ruled out against Italy, with Joe Worsley and Alex Sanderson providing clear alternatives in Back's possible absence.
But it looks as if Wilkinson, England's key man with 36 of his team's 51 points in the championship to date, will make the Italy encounter after suffering a knee problem.
"I came off as a precaution at the end, and it feels a lot better now," said Wilkinson.
Saracens director of rugby Mark McCall believes Alex Lozowski has only just scratched the surface of his potential after the 23-year-old celebrated his England recognition by scoring a try-double against Bristol.