However, a medical scan has revealed the injury is not as bad as first thought and, though Halfpenny will miss the England match and probably the trip to Scotland the following Saturday, he should make his return in a matter of weeks.
"Leigh has an acute sprain to his ankle, but the scan has revealed no further disruption to the ligaments, which is much more positive news than was first feared," said Wales team physiotherapist Mark Davies.
"He will wear a boot and stay off his feet for the next few days, but will remain in camp where we will monitor his rehab.
"The injury rules him out of the England game and should mean he misses the visit to Scotland."
The Wales management did consider calling in cover for Halfpenny, but have decided not to add to the 28-man squad at this time whilst continuing to monitor his progress.