England defenders Kyle Walker and Harry Maguire, and back-up goalkeeper Sam Johnstone, have been ruled out of Tuesday’s friendly with Belgium.
Burnley keeper James Trafford and Manchester City defender Rico Lewis, who were with the England Under-21s, have been promoted to the senior squad.
Trafford, 21, helped England win the Euro Under-21 last summer and this is his first senior call-up.
Lewis, 19, made his Three Lions debut in November against North Macedonia.
His City team-mate Walker was injured in the first half of Saturday’s 1-0 friendly defeat by Brazil at Wembley.
Manchester United’s Maguire, who replaced Walker as captain when he was substituted, came off in the 67th minute.
Maguire, Walker and Crystal Palace’s Johnstone, 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 first-choice striker, gives a chance to Ollie Watkins and Ivan Toney to impress.
Aston Villa’s Watkins played against Brazil, with Brentford forward Toney set to feature in the Belgium game.
“It would be his first start, so you’ve got to bear that in mind as well,” said Southgate about Toney.
“With England that’s the landscape, you don’t get hundreds of opportunities. I think every player recognises that’s the world we live in.
“But he’s a confident guy, he comes in on the back of a good run of form with his club. He’s going to be on the field on Tuesday, no question.
“That swagger, that self-belief is crucial – all of the top forward players have it. I think sometimes the quality of his football can be underestimated.
“His passing, his link play. We’re still getting to know all of those strengths because until you work with a player more regularly you don’t know them inside out.”
