Declan Rice has added to England's growing casualty list after pulling out of their World Cup qualifiers.
West Ham midfielder Rice has left St George's Park with illness having been unable to train since reporting up which means they are without five players from the original squad.
England boss Gareth Southgate is also set to be without Mason Mount and Luke Shaw for Friday's showdown with Albania at Wembley.
They have already seen Marcus Rashford and James Ward-Prowse pull out which leaves them with 21 players, having called up Arsenal youngster Emile Smith Rowe.
Southgate is not planning to make any additional call-ups but if they lose any more players then he may yet bring in another name.
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Chelsea midfielder Mount had dental surgery on Sunday to remove four wisdom teeth and has yet to join up at St George's Park but may still go to San Marino.
Manchester United left back Shaw is also following concussion protocol after getting injured in the Manchester derby last weekend. Chelsea's Ben Chilwell is set to play against Albania but Shaw is hoping to join up.
Southgate now faces a dilemma in midfield as to whether to play Jordan Henderson or Jude Bellingham alongside Kalvin Phillips or even drop Phil Foden deeper.
They still need a result against Albania and will go as strong as possible as they look to clinch qualification but may be able to rest players in San Marino for an easier fixture but they still cannot clinch their place on Friday.
Although Southgate will be without several players for England's next fixture, the manager will be glad to have Chelsea defender Reece James at his disposal.
James has been in sensational form this season, scoring eight goals and producing three assists in the Premier League, but missed the October internationals through injury.
Discussing his recent form, the 21-year-old said: "This is probably the best I have performed. At this moment in time our team is performing well and creating a lot of chances, so it's obviously helping.
"When you are playing week in and week out, and you are playing well and the team is performing, keeping clean sheets and winning games in style, it obviously helps build everyone's confidence."
Many England fans will be keen to see Smith Rowe get his chance after making an impressive start to the season, scoring the winner in Arsenal's recent Premier League victory against Watford.
Discussing his first senior call-up, the player said: "It was a great moment for me and my family - I ran downstairs straight away and told my mum.
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"It was very emotional. They were so proud of me... It still hasn't sunk in I'm actually here yet."
Two players who aren't included in Southgate's squad for the crucial qualifiers are Jesse Lingard and Jadon Sancho, who are both lacking Premier League minutes at Man Utd.
Explaining his decision to omit the players, the manager said: "They [Lingard and Sancho] know that at the moment they've got to get playing for their clubs and playing well."