Liverpool captain Jordan Henderson and Manchester City duo Fabian Delph and Raheem Sterling have all pulled out of the England squad, increasing the number of withdrawals from Gareth Southgate's original 25-man group for a friendly double-header against Germany and Brazil to six.
Henderson was due to start for Liverpool during a comprehensive 4-1 victory over West Ham United on Saturday evening (4 November) after complaining of discomfort in his thigh muscle following a routine training session at Melwood. However, he was later left out entirely by Jurgen Klopp on the advice of his medical department.
The 27-year-old was not due to travel to St. George's Park until later this week anyway, although the Football Assocation (FA) confirmed on Tuesday morning that he had now withdrawn from contention.
The former, who has been deployed in a left-back role by Pep Guardiola in the absence of Benjamin Mendy, lasted the entirety of a 3-1 win at the Ethihad Stadium while winger Sterling was replaced by Ilkay Gundogan after 78 minutes.
The loss of that trio will come as another key blow to Southgate, who was already without Dele Alli due to a hamstring injury sustained during Tottenham Hotspur's memorable Champions League defeat of Real Madrid last week.
Spurs teammates Harry Winks and Harry Kane also pulled out on Monday evening due to respective ankle and knee issues sustained against Crystal Palace. Henderson, who may now be considered as a doubt for Liverpool's next top-flight fixture against Southampton on 18 November, and Kane had been rotating the senior England captaincy over recent months.
England have already drafted in Everton centre-back Michael Keane and West Bromwich Albion midfielder Jake Livermore as replacements and a further squad update sure to include more new faces is due to be confirmed later today.
The squad already contains three uncapped players in Chelsea duo Tammy Abraham and Ruben Lofus-Cheek - on loan at Swansea City and Crystal Palace respectively - and versatile Liverpool defender Joe Gomez.
The likes of Ashley Young, Danny Rose and Jamie Vardy earned recalls, while Alex Oxlade-Chamberlain, Daniel Sturridge and Jack Wilshere were among the most high-profile absentees. Liverpool pair Nathaniel Clyne and Adam Lallana were already unavailable due to injury, as were Danny Welbeck and Tom Heaton.
One piece of good news amid the gloom for Southgate surrounds Gary Cahill, who has reported for international duty as planned and is scheduled to take part in a 21-man training session this afternoon. The experienced centre-back underwent an assessment by Chelsea's medical team following their 1-0 victory over Manchester United at Stamford Bridge.
England entertain reigning world champions Germany on Friday evening before welcoming top Conmebol World Cup qualifiers Brazil to Wembley Stadium four days later.