Manchester City pair John Stones and Fabian Delph and Chelsea midfielder Ruben Loftus-Cheek have all withdrawn from the England squad for this month's Euro 2020 qualifiers against Czech Republic and Montenegro as a result of injuries.
Southampton midfielder James Ward-Prowse has already been called in as a replacement, although it remains to be seen whether others will also be drafted in as manager Gareth Southgate had initially named a larger than normal 25-man squad.
Stones was the second most capped defender in the squad behind only clubmate Kyle Walker, while Delph made his international debut back in 2014 and played his way back into the Three Lions setup last year after an injury ravaged period in the wilderness.
Loftus-Cheek only made his senior England debut last season during a successful loan spell at Crystal Palace. But his place in the squad this time around had been questioned as a result of starting just one Premier League game for Chelsea all season.
England will kick off the journey to Euro 2020, the final of which is to be held at Wembley, this coming Friday when Czech Republic visit in the opening qualifier. The team will then travel east to face Montenegro in Podgorica on Monday.
Bulgaria and Kosovo are the other two countries in England's qualifying group.
After March, England's next games will be played in June when they contest the inaugural UEFA Nations League Finals after topping League A Group 4.
The four-team tournament will see England take on Netherlands in a semi final on 5th June, with the winner facing either Switzerland or Portugal in the final four days later.
For England, it could be a first major international trophy since World Cup glory in 1966.