Lock Ollie Chessum has been ruled out of England's Six Nations finale against Ireland in Dublin after suffering an ankle injury in training.
Leicester team-mate George Martin has been called up to the squad.
Experienced backs George Ford and Manu Tuilagi remain in contention to make their returns after being named in the 30-man squad.
England face Grand Slam-chasing Ireland at the Aviva Stadium at 17:00 GMT on Saturday.
Chessum has started all four of England's Six Nations matches so far in the second row, but is now set for a lengthy spell out of action.
"Really disappointed, he's been outstanding for us throughout this campaign," assistant coach Kevin Sinfield told BBC Sport.
"He's a big loss for us. So our thoughts and wishes are with him and we hope for a speedy recovery."
Chessum's absence means England now have to make at least two changes from the side thrashed 53-10 by France last weekend, with centre Ollie Lawrence also injured.
"What we've tried to do with selection throughout this campaign is pick the team that we believe gives us the best chance of winning, that was always going to be the case for this weekend as well," Sinfield added.
"You are balancing that up with rewarding lads who have played well but also giving lads another chance after what we dished up on Saturday.
"We know we need to be a whole lot better."
'It's still raw - there is some grief'
England were giving a stark reality check by the French, shipping seven tries in their heaviest ever Twickenham loss, and Sinfield admits the hurt of that defeat still lingers a few days later.
"It's still raw and there's still some grief around," Sinfield added.
"There is a lot of grief, because it's not nice, because there's a lot of negative emotions and disappointment and embarrassment all wrapped up.
"When anyone puts 50 on you it hurts and it should, so we've worked incredibly hard at trying to understand why and then try and help take us forward.
"We came up against a team that were red hot, and I think it shows the gulf that is in play at this moment in time, a gulf we are trying to close as quickly as we can.
"The challenge for us now is we play the best team in the world currently, but I don't think there is a better opposition to come up against for us, another real challenge to see what character we have about us and to see if we can respond.
"We will learn a lot about ourselves on the weekend, it is certainly a tight group and I've been really impressed with how the players have responded."
Sinfield has confirmed Ford and Tuilagi are both fit, match sharp, and ready for selection as England plot a way to recover from their Twickenham nightmare and upset the odds at the Aviva.
"We knew this wasn't going to straightforward or an easy fix. At the minute it is clear to see there is a gulf.
"But throughout my own career there were a lot of results and performances like we got on Saturday, and they can be quite big on changing this next path.
"Although it's horrible at this moment in time, it could turn out to be quite a big moment for us."