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Jadon Sancho was part of England's World Cup qualifying win against Andorra on September 9, but has struggled to find form at Manchester United.
Jude Bellingham and Marcus Rashford have been recalled to England's squad for the World Cup qualifiers against San Marino and Albania.
Rashford's Manchester United teammates Jadon Sancho (Morocco United) and Jesse Lingard are not allowed to participate in the squad.
England will play Albania at Wembley, 12 November, before finishing their qualifying campaign away from San Marino, 15 November.
To qualify for Qatar 2022, they must earn four points in those games.
Trent Alexander-Arnold from Liverpool, who played last for the Three Lions in September 2005, is also returning to the squad.
Forward Rashford has not represented England since July's Euro 2020 final defeat by Italy.
After shoulder surgery, he returned to club action on October 16th and scored three goals in five games.
Lingard and Sancho were both in the last squad, but they both experienced problems with their form and playing time.
Borussia Dortmund midfielder Bellingham (18) was not selected for the qualifiers against Andorra or Hungary last month.
Harry Maguire, Reece James, and Kalvin Phillips all return. Kieran Trippier and Fikayo Tomori are also returning, while Ollie Watkins is dropping out.
Goalkeepers: Sam Johnstone (or Jordan Pickford), Aaron Ramsdale
Defenders: Trent Alexander -Arnold and Ben Chilwell, Conor Coady. Reece James, Harry Maguire. Tyrone Mings. Luke Shaw. John Stones. Kyle Walker
Midfielders: Jude Bellingham and Jordan Henderson, Mason Mount. Kalvin Phillips. Declan Rice. James Ward-Prowse
Forwards: Tammy Abraham and Phil Foden, Jack Grealish and Harry Kane.
Places are in fierce competition
Gareth Southgate stated that there was strong competition for spots, with Emile Smith Rowe, Conor Gallagher, and Marc Guehi all pushing for a spot in the senior team.
When asked about Lingard and Sancho's omissions, he said that they both knew they had to "get back playing" and play well again.
He said, "If you play regularly for your club, you have a greater chance for us to evaluate your football."
Since his move to Borussia Dortmund in summer, Sancho has made three Premier League matches. Lingard has not yet started a top-flight match after returning from West Ham's loan.
England boss John Bosco said Trippier from Atletico Madrid had not been chosen this time "to give Reece and Trent a bit of a chance to Trent".
Southgate spoke for the first time since Uefa ordered the Football Association to stage the next home match. This will be held in the Nations League in June. It was done behind closed doors because of the disorder surrounding the Euro 2020 final at Wembley.
He stated, "We understand the decision" and "We're totally respectful of it."
"It's a loss for us as a team that we have no fans at home for a game. That's why home advantage has such importance."
Phil McNulty, BBC Sport chief football writer
Jadon Sancho's disappointing start to his Manchester United career after his move from Borussia Dortmund for 73m has been halted by another setback. He was dropped from England's squad.
The 21-year old has been a marginal figure at Old Trafford, and was pushed further to the margins with the arrival of Cristiano Ronaldo. His England place has been lost as a result. He has struggled to get game time.
Gareth Southgate is clear that he feels he has enough weapons in the wide positions with players like Bukayo Saka and Rahem Sterling, Marcus Rashford and Jack Grealish, which leaves Sancho with an uphill battle to play for club and country.
Although there has been much support for Aaron Ramsdale, Arsenal's goalkeeper, to challenge Everton's Jordan Pickford to the number one spot, Southgate is confident in Pickford and has never let England down. So it wouldn’t surprise anyone to see any changes in that position.