Harry Kane, Raheem Sterling, Fabian Delph, Jordan Henderson, Dele Alli and Harry Winks have already pulled out of the squad.
Washington-born stopper Pickford, who joined Everton from Sunderland last summer, is believed to be starting in goal with Gareth Southgate reportedly looking to hand debuts to Tammy Abraham and Ruben Loftus-Cheek also.
England qualified easily in a campaign that saw a managerial change and more than 40 players tried out in a whole host of different formations as Gareth Southgate continues to search for that winning formula that will finally end 51 years of hurt.
England hosts world champions Germany at Wembley today and Brazil on Tuesday.
Joachim Low's charges were the only team to win all 10 of their qualifiers in Europe; together with their success at the Confederations Cup and the European Under-21 Championship in the summer, there is little to suggest German football is on the wane.
"This period between qualification and the finals has to have an element of experimentation", Southgate told a news conference on Thursday.
"I've really enjoyed the week". They are injured and they can't play.
Southgate dismissed any talk of a club-versus-country row over players' fitness.
England continue their preparations for the 2018 World Cup with a high-profile friendly against Germany at Wembley.