Lee Carsley wants the England players at his disposal to "make the most of the situation" after nine others dropped out through injury.
Everton defender Jarrad Branthwaite on Wednesday became latest player to withdraw from the Nations League games with Greece and Republic of Ireland.
Trent Alexander-Arnold, Cole Palmer, Phil Foden, Jack Grealish, Bukayo Saka, Declan Rice, Aaron Ramsdale and Levi Colwill have also dropped out.
England captain Harry Kane has admitted to being unhappy with the large number of withdrawals for interim boss Carsley's final two games in charge.
However, Carsley attempted to put a positive spin on the situation when speaking at his pre-match press conference on Wednesday ahead of facing Greece.
"The focus all camp has been on the players that are here and it's important that we make the most of the situation," he told reporters.
"With the amount of players that have pulled out, it gives other players an opportunity to be here.
"We're really looking forward to the game and it's going to be a tough test for us and the focus has been purely on the players that are here.
"With the amount of pull-outs we've had in the window, historically it's been like that in the past - November has always been a challenging window.
"But the culture that Gareth [Southgate], Steve [Holland] and the rest of the lads created has made it a really positive environment and the players that are here thoroughly deserve to be here."
Grealish was one of the first players to withdraw from the squad, having been called up despite not playing for club side Manchester City since 20 October.
City boss Pep Guardiola questioned England's decision to include Grealish in their squad as he recovers from injury, but Carsley insisted he was justified in doing so.
"The medical teams are constantly talking throughout squad selection, regardless of whether there are games or not," Carsley said.
"We are constantly getting updates. The medical departments have brilliant communication between club and country.
"It was always the case we were going to get the players who were potentially going to miss out in to the assessed. Jack was one of them. He was assessed and sent back and it was as clear as that."
England trail Group B2 leaders Greece by three points with two rounds of fixtures to play, having lost the reverse fixture 2-1 at Wembley last month.
The Three Lions have won on all four of their previous trips to face Greece, doing so by an aggregate score of 9-1 - only against Luxembourg (5/5) do they hold a better 100% win rate away from home.
However, Greece are on the longest active winning run of any European nation in all competitions (five games) and could win six consecutive matches for the first time November 2013.
Carsley, who will step aside for Thomas Tuchel after next week's home match with Republic of Ireland, said: "We're expecting a tough game against Greece and it’s one we have to win.
"But we're really looking forward to it, we've had a good week's training, the players are in good spirits and it's going to be a sell out with a great atmosphere.
"We've had to wait four or five weeks for this, but this next window is so important to us, not just tomorrow but Republic of Ireland as well, so it's a great challenge for us."