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England defenders Kyle Walker and Harry Maguire, and reserve goalkeeper Sam Johnstone, have been ruled out of Belgium's friendly match on Tuesday.
Burnley goalkeeper James Trafford and Manchester City defender Rico Lewis, who were both with the England Under-21s, have been promoted to the first team.
Trafford, 21, helped England win the European Under-21 Championship last summer and this is his first call-up to the first team.
Luis, 19, made his debut for the Three Lions in November against North Macedonia.
Manchester United's Maguire, who replaced Walker as captain when he was substituted, was subbed off in the 67th minute.
Crystal Palace's Maguire, Walker and Johnston, who did not feature on Saturday, have returned to their clubs.
Bayern Munich striker Harry Kane and Arsenal winger Bukayo Saka have already been ruled out.
The injury to Kane, undoubtedly England's number one striker, gives Ollie Watkins and Ivan Toney a chance to impress.
Aston Villa's Watkins played against Brazil, and Brentford striker Toney is set to feature against Belgium.
“This will be his first start, so you have to keep that in mind as well,” Southgate said of Toney.
“With England, that's the landscape, you don't get hundreds of chances. I think every player understands that this is the world we live in.
He added: “But he is a confident man, and this comes on the back of his good form with his club. He will be on the field on Tuesday, without a doubt.”
“That swagger and self-confidence is crucial – all great attacking players have it. I think sometimes the quality of football he plays can be underestimated.
“His passing, his connections to the game. We're still getting to know all those strengths because until you work with a player on a more regular basis, you don't know him that well.”
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