Wales suffered a major setback hours before their Six Nations meeting with England after full-back Leigh Halfpenny was ruled out of the Twickenham clash.
Halfpenny missed the captain’s run on Friday, apparently through illness, but Warren Gatland hoped he would be available to start their second match in the tournament.
However, the Scarlets No 15 will not start because of a foot infection which has caused significant swelling, and his place will be taken by Gareth Anscombe.
Owen Watkin moves on to the replacements bench with Gatland opting not to recall Liam Williams back from Saracens.
Rhys Patchell could take over kicking duties from Halfpenny, who was the star performer for Wales in their 34-7 win over Scotland last Saturday.
Warren Gatland says Wales must avoid being intimidated by the Twickenham factor when his side face England in the Six Nations on Saturday
Halfpenny scored two of Wales’ four tries and kicked a further 14 points to inspire his team to victory at the Principality Stadium.
Anscombe, who will be starting only his seventh international game, plays more of his rugby at fly-half but does have plenty of experience at 15.
Halfpenny is the latest in a long line of experienced Wales stars to be missing, joining Sam Warburton, Taulupe Faletau, Jonathan Davies, Rhys Webb and Williams on the sidelines.