Fikayo Tomori has been called up to the England squad for upcoming October World Cup qualifiers, while Phil Foden and Ollie Watkins return after injuries.
With numerous key players out with injury for the upcoming international break, England manager Southgate has opted the AC Milan defender who picked up his sole cap against Kosovo in a Euro 2020 qualifier in November 2019.
Southgate says he has been impressed with the 23-year-old's performances for AC Milan since joining the Serie A club in January.
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"I like Fikayo (Tomori) in terms of his aggressiveness of defending," Southgate said in his England press conference.
"He's got speed he's confident enough to defend on the front foot and he's improving on the ball as well.
"I have been very impressed. I thought he finished last season well. We were tracking him well last season and he is playing well this season.
"He is at a club that's expected to win every week, I thought he did well against Liverpool and Juventus."
Reece James has also been included in the squad despite missing Chelsea's Champions League defeat to Juventus on Wednesday night with an ankle problem.
Mason Mount, who has also struggled with injury recently, has been included as well as Luke Shaw who limped out of Manchester United's 1-0 defeat to Aston Villa last Saturday.
Arsenal goalkeeper Aaron Ramsdale has been called up ahead of Burnley's Nick Pope.
Harry Maguire has a calf injury while Trent Alexander-Arnold is also out. Dominic Calvert-Lewin has a fractured toe, Patrick Bamford has a damaged ankle while Marcus Rashford is still out after having shoulder surgery.
Manchester United's Mason Greenwood, Borussia Dortmund's Jude Bellingham and Arsenal duo Ben White and Emile Smith Rowe all miss out on places.
Southgate says Smith Rowe, 21, was close to getting called up.
He added: "He is a player we like a lot and was very close to making this squad.
"At this moment in time I don't want to bring in any more younger players out of the Under-21s. They have got to earn that right over a longer period.
"I thought his performance against Tottenham was very good, we know how he finished last season as well. I can only say he is a player we really like and he was close."

FULL ENGLAND SQUAD

Goalkeepers: Sam Johnstone (West Brom), Jordan Pickford (Everton), Aaron Ramsdale (Arsenal)
Defenders: Conor Coady (Wolves), Reece James (Chelsea), Tyrone Mings (Aston Villa), Luke Shaw (Manchester United), John Stones (Manchester City), Fikayo Tomori (AC Milan), Kieran Trippier (Atletico Madrid), Kyle Walker (Manchester City)
Midfielders: Phil Foden (Manchester City), Jordan Henderson (Liverpool), Jesse Lingard (Manchester United), Mason Mount (Chelsea), Kalvin Phillips (Leeds), Declan Rice (West Ham)
Forwards: Jack Grealish (Manchester City), Harry Kane (Tottenham), Bukayo Saka (Arsenal), Jadon Sancho (Manchester United), Raheem Sterling (Manchester City), Ollie Watkins (Aston Villa)
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