Trent Alexander-Arnold, Ben White, Ben Godfrey and Aaron Ramsdale have all been named in England's provisional 33-man squad for Euro 2020, but Eric Dier misses out.
There is a first senior call-up for Brighton centre-back White and Everton defender Godfrey, while Sheffield United goalkeeper Ramsdale joins uncapped Sam Johnstone in the squad as Nick Pope misses out through injury.
Southgate has named a 33-man group that will be trimmed down to 26 players on June 1, allowing him to include injury doubts such as Harry Maguire, Jordan Henderson and Kalvin Phillips.
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Tottenham's Eric Dier misses out on the Euro 2020 squad, but Alexander-Arnold returns to the group alongside fellow right-backs Reece James, Kieran Trippier and Kyle Walker.
Bukayo Saka, Ollie Watkins, Mason Greenwood and 17-year-old Jude Bellingham are among the others to get the nod.
Jesse Lingard is in the expanded squad after his impressive form for West Ham since joining on loan from Manchester United in January, but there is no space for Leeds United's Patrick Bamford, who scored 17 Premier League goals this season, or Southampton's Danny Ings.
England face warm-up friendlies against Austria on June 2 and Romania on June 6, before kicking off their tournament against Croatia on June 13.
Speaking about his decision to name a 33-man squad, Southgate explained: "Really I think our situation is more complicated than any other country at the moment.
"Of this 33, 12 are still to play in European finals this week so we were always going to need some additional players for the first part of our camp.
"Add into that we have injuries at various stages, there are a couple we have very little information about and a couple who are back into training and matches in Jordan Henderson and Jack Grealish but not training consistently.
"We felt that more time is going to help us make better decisions.
"I've always said my preference would be to name the squad as a clean 26, we did that in Russia and we had standby players who knew their roles and that's always a preferable situation.
"But we haven't got an ideal hand of cards this time and there are a lot of unknowns and I think information and evidence is really important when you're making decisions, we'll have more in the next seven days."
England's provisional 33-man squad for Euro 2020:
Goalkeepers: Dean Henderson (Manchester United), Sam Johnstone (West Brom), Jordan Pickford (Everton), Aaron Ramsdale (Sheffield United).
Defenders: Trent Alexander-Arnold (Liverpool), Ben Chilwell (Chelsea), Conor Coady (Wolves), Ben Godfrey (Everton), Reece James (Chelsea), Harry Maguire (Manchester United), Tyrone Mings (Aston Villa), Luke Shaw (Manchester United), John Stones (Manchester City, Kieran Trippier (Atletico Madrid), Kyle Walker (Manchester City), Ben White (Brighton).
Midfielders: Jude Bellingham (Borussia Dortmund), Jordan Henderson (Liverpool), Jesse Lingard (West Ham), Mason Mount (Chelsea), Kalvin Phillips (Leeds), Declan Rice (West Ham), James Ward-Prowse (Southampton).
Forwards: Dominic Calvert-Lewin (Everton), Phil Foden (Man City), Jack Grealish (Aston Villa), Mason Greenwood (Manchester United), Harry Kane (Tottenham), Marcus Rashford (Manchester United), Bukayo Saka (Arsenal), Jadon Sancho (Borussia Dortmund), Raheem Sterling (Man City), Ollie Watkins (Aston Villa).
'Dier's season not strong enough'
Tottenham's Dier played a key part in the England side who reached the semi-final of the 2018 World Cup in Russia, and had become a regular member of the squad under Southgate.
But the England boss says the 27-year-old's performances for Spurs this season means he cannot justify selecting him ahead of players in better form.
"He is a man who I have tremendous respect for and he has been a key player in some of our biggest games and biggest moments," he said.
"Unfortunately I just don't think his season has been strong enough to be in the squad and that is a difficult call because I know how much he brings to the whole group.
"When you are at a tournament the players who put the team first are critical. It wasn't an easy conversation but he is an outstanding professional and took the news in a professional way."
'People think I'm obsessed with right-backs - I just see four good footballers'
Southgate refused to be drawn on his selection at right-back, as Liverpool's Alexander-Arnold returned to the England setup following his omission from a recent squad.
When asked if he felt Alexander-Arnold had done enough to impress him in the final part of the season, Southgate responded: "I could easily get drawn into talking about any number of individuals that might be in the 26, and then I'm going to get myself in the mess.
"You're looking at four right-backs, people feel I have an obsession with right-backs - I just see four good footballers.
"Trippier can play right or left-back, Trent can play right-back, wing-back, I think he can play in midfield. In the last few days I've seen Reece James right of a three, at wing-back, in the middle of midfield.
"We're going to a tournament and those sort of flexible players who can fulfil different roles but are good footballers are going to be hugely important to us. So we really don't know how the next few weeks will play out in terms of availability, injuries, what our best systems will be with the people we have available. We've got too many question-marks as I sit here today, but that will become far clearer. We know what we'd like to do, and we have good contingencies in place."
'Kane future will be resolved after Euros'
Harry Kane's future has been the subject of much speculation after he signalled his desire to potentially leave Tottenham to win major honours, but Southgate does not think a move away from Spurs will happen before the end of the Euros.
He said: "I don't need to talk about Harry Kane's focus or professionalism. He has got one goal with us and that's to win a European Championship.
"What is going on at his club is a matter for him and Tottenham. He has made some statements in the last few days but that is out of the way now and I think it is very unlikely transfer deals will be done while we are away.
"We are not going to stop phone ringing and cannot control conversations going on in private. Most deals are done after tournaments or in September, I would expect any deals to be done after the tournament."
'Konsa and Tomori were in contention'
Southgate also revealed that Aston Villa's Ezri Konsa and AC Milan's on-loan Chelsea centre-back Fikayo Tomori were both in contention to be named as an option in central defence.
When asked if he felt he was taking a risk named the previously uncapped pair of White and Godfrey, Southgate replied: "The private conversations I've had with players, I'm not going to go into too much.
"I think they're both exciting young defenders. There are others we've also been looking at who we really like. Ezri Konsa has had a good season at Aston Villa, Fikayo Tomori has done well at Milan.
"These two [White and Godfrey] are very flexible. They can play in different roles as well - left, right, midfield in White's case. This is a great opportunity for us to get to know them a bit better.
"There's no way of knowing how long they'll be with us, but it should be a fantastic experiences."
'Same time next week, Gareth?'
Analysis from Sky Sports News reporter Rob Dorsett...
That was the overriding emotion after the England manager named his provisional squad for the upcoming Euros. 33 names that he must whittle down to 26 by June 1, when the list must be formally submitted to UEFA.
The fact is, it's the removal of seven names from the group that will be most telling.
Southgate was completely correct to call a halt and buy himself some time before making the final decision. May 25 was an arbitrary date, pulled from the calendar by the FA, because it suited media duties and fitted with other commitments.
But England can make changes to their Euros squad right up until their first game on June 13 against Croatia, so it made no sense to name 26 players now, almost three weeks before that date, with so many uncertainties still to be answered.
How fit are Harry Maguire and Jordan Henderson? How much game time can they have and how quickly? How will the 12 England players taking part in this week's European finals react? Until those questions are answered, Southgate simply could not make a qualified judgement.
In any other squad announcement, first call ups for Brighton's Ben White and Everton's Ben Godfrey would have got all the headlines. However, it's almost inevitable that - unless horrific injury problems ensue - they will both be omitted from the final 26.
There's an interesting discussion about whether it will be Sam Johnstone or Aaron Ramsdale who get the nod - but, in reality, you're talking there about England's third-choice goalkeeper who probably won't get any game time in the tournament.
And crucially, the key issues remain unaddressed and have been kicked down the road for a week. There are four right-backs in this extended squad - so will Trent Alexander-Arnold make the final reckoning? If he does, who out of Reece James, Kieran Trippier and Kyle Walker will miss out?
Will either Jesse Lingard or Mason Greenwood beat the final cull? Will Henderson, Maguire and Kalvin Phillips be fit enough to play a part in the tournament from the start, or indeed as it progresses?
How much time off will each of the 12 players involved in the Europa League and Champions League be given, and when will they actually join up with the rest of the England squad?
Key questions, yet to be answered. The omissions of Eric Dier and Danny Ings were telling - it looks a long road for both of those to get back into an England squad as things stand.
But the big decisions will be made by Southgate and his staff in the next week. England's squad for the Euros has yet to take shape.