Crystal Palace pair Marc Guehi and Tyrick Mitchell and Southampton full-back Kyle Walker-Peters could make their England debuts in the friendly against Switzerland on Saturday.
The defensive trio were called up to the senior team by manager Gareth Southgate for the first time.
Emile Smith Rowe is unlikely to feature in the friendly at Wembley (17:30 GMT) after missing training on Friday.
Southgate said it was a “shame” to lose Bukayo Saka because of Covid.
The Arsenal midfielder had been isolating from the rest of the squad at St George’s Park since Wednesday, but returned home on Thursday.
Centre-back Guehi was named in the original squad but Mitchell and Walker-Peters were late call-ups after the withdrawals of Liverpool’s Trent Alexander-Arnold and Chelsea’s Reece James.
Southgate said: “We will have debuts this week for sure. Great moments for those players and we will always want to put them in with experienced players.
“Training has been good. The players have enjoyed being back together with their England team-mates.
“It has given them a psychological refresh before they go back into another important period with their clubs and we are enjoying working with them again.”
England continue their preparations for the World Cup, hosting Switzerland before another home friendly against Ivory Coast on Tuesday (19:45 BST).