England's Alex Mitchell will miss the game against Scotland after sustaining a knee injury in training.
It's a huge blow for head coach Steve Borthwick that the Northampton Saints player has been his first choice for scrum-half over the past few months.
Mitchell impressed as the Red Rose reached the Rugby World Cup semi-finals and continued their form into the 2023/24 season.
Starter from the opening game
As a result, he started in the first round of the Six Nations against Italy and Wales, and was selected for round 15 of the Calcutta Cup.
However, he will definitely miss this matchup, and the full prognosis is not yet determined. The Rugby Football Union said further reviews were needed to determine a date for his return.
Bristol Bears livewire halfback Harry Randall has been named as Mitchell's replacement and will compete for a place in the top 23 with Danny Care and Ben Spencer.
Elsewhere, there was good news for England, with Olly Lawrence good enough to be selected in the updated 36-man squad.
Lawrence is nursing a hip injury and was not considered fully recovered when Borthwick named him to the training group a few days ago, but he has made good progress since then.
Center conundrum
This means Fraser Dingwall could be left out of the 23-man squad for the game against Scotland at Murrayfield, given that Bath center and Manu Tuilagi are both available.
Dingwall started the first two games and scored his first Test try against Wales, but Borthwick may need a little more out-and-out power in that slot.
Coach Borthwick will name his team for Thursday's match as the Red Rose aim to improve to 3-3 in the tournament.
So far, they have defeated Italy and Wales in 2024, but the Scots are currently on a three-game winning streak against England.
England have won just one of their last six meetings with Scotland, with their last success coming at Murrayfield in 2020.
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