It represents a major worrry for England manager Gareth Southgate, as well as their clubs, ahead of their upcoming World Cup qualifiers.
As key defenders, the knocks could be a massive blow for all parties concerned.
It remains to be seen what the extent of the injuries are for the England star but with the international break so close, their participation for the Three Lions is a doubt.
The Chelsea youth product, who was seen clutching his ankle, will be even more disappointed with the outcome given the start to the season he's had.
He showcased his quality in the Blues' dominant win against Arsenal earlier in the season scoring and assisting in a 2-0 win at the Emirates however on the flip side, he was sent off against Liverpool and will now have to deal with this latest setback.
Although it's a blow for James, England are blessed with several outstanding right-backs and should be able to get through.
Left-back, however, is a different story.
Throughout Euro 2020, Shaw was a vital component as the Three Lions reached their first international tournament final since 1966.
A goal and three assists showcased his talents and Southgate, who was at the game, will certainly miss him should he fail to recover in time.
Meanwhile, Maguire, who appeared to have a calf issue, is another Southgate would have a tough time to replace in key games.