Raheem Sterling, Fabian Delph and Jordan Henderson are the latest withdrawals from England's injury-hit squad for friendlies against World Cup holder Germany and five-time winner Brazil, the FA said Tuesday.
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Gareth Southgate's men kick off their World Cup preparations with back-to-back Wembley matches against the international heavyweight teams over the coming week.
Tottenham's Dele Alli, Harry Kane and Harry Winks have already withdrawn from the initial 25-man squad, with England receiving three further setbacks on Tuesday.
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"Manchester City duo Raheem Sterling and Fabian Delph have returned to their club after being ruled out of England's forthcoming fixtures," a statement from the Football Association read.
"Liverpool's Jordan Henderson will also miss out on the back-to-back games against Germany and Brazil at Wembley Stadium through injury."
Henderson had been due to arrive at St George's Park - England's training base - later in the week after missing Liverpool's win against West Ham with a thigh problem.
City winger Sterling is out with a back complaint and Delph - looking for his first England cap since November 2015 - injured his calf towards the end of Sunday's win against Arsenal .
Alli, Kane and Winks have already pulled out with injury issues of their own, with Southgate bringing in Michael Keane and Jake Livermore.
More faces will likely be drafted in by the England boss ahead of Friday's friendly against Germany, with the FA announcing "a further squad update will be issued in due course" but Chelsea defender Gary Cahill is set to train on Tuesday.
England, which plays Brazil on November 14, is already missing Adam Lallana, Danny Welbeck, Nathaniel Chalobah, Tom Heaton and Ross Barkley.
Southgate had plumped for a bold squad for the last matches of 2017, with Tammy Abraham, Ruben Loftus-Cheek and Joe Gomez called up for the first time as Daniel Sturridge, Alex Oxlade-Chamberlain and Chris Smalling were overlooked.
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