KOBBIE MAINOO, Ezri Konsa and Morgan Gibbs-White have all withdrawn from England's squad for the upcoming Uefa Nations League games.
The Three Lions host Greece at Wembley on Thursday before heading to Finland on Sunday, in Lee Carsley's second round of fixtures.
The trio drop out after sustaining injuries for their respective clubs over the weekend in what is a triple injury blow for Carsley's new-look side.
Konsa, 26, suffered a hamstring injury and left the pitch just 12 minutes into Villa's goalless draw with Manchester United.
And Gibbs-White, 24, was removed after 76 minutes of Nottingham Forest's 1-1 draw at Chelsea.
But Mainoo played 85 minutes at Old Trafford on Sunday before he was replaced by Casemiro.
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It comes as a further blow for under-fire boss Erik ten Hag who also lost the services of Harry Maguire, who left Villa Park in a plastic boot.
Maguire was dropped from Carsley's squad after featuring in September and Mainoo has been carrying a knock for some time.
The 19-year-old midfielder was subbed off shortly before half-time during Man Utd's 3-0 demolition at the hands of Spurs a fortnight ago.
Mainoo travelled to Portugal with the Red Devils on Thursday as they drew 3-3 with Porto, but missed the game with a minor issue.
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Meanwhile Carsley handed Konsa a starting role when the Three Lions beat Finland 2-0 at Wembley on 10 September.
Gibbs-White made his senior debut for England from the bench during their 2-0 victory against the Republic of Ireland on 7 September.
Forest manager Nuno Espirito Santo suggested the prognosis on Gibbs-White is unclear until they further investigate this week.
Mainoo started against Ireland but did not feature against Finland.
All other 22 players are at St George’s Park with no further additions planned at this time.
Harry Kane was a serious doubt but he has since been cleared to play after arriving to the Burton-on-Trent base earlier today.
He could line up alongside new dad Jack Grealish, who announced he his baby news from St George's Park.
England currently sit second in their League B Group 2, only behind leaders Greece on goal difference.