England captain Harry Kane and midfielders Cole Palmer and Jordan Henderson will all miss Saturday’s game with Brazil at Wembley.
It is the first of two home friendlies for England, with a game against Belgium to follow on Tuesday.
“I would say Cole and Hendo have a better chance for Belgium than Harry – he’d be extremely doubtful for that,” said England boss Gareth Southgate.
“It’s a brilliant opportunity for other players.”
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The injury to England’s all-time top scorer Kane could give either Aston Villa striker Ollie Watkins or Brentford’s Ivan Toney a rare opportunity to impress in the final England games before the Euro 2024 warm-up games in June.
Watkins, with 16 goals and 10 assists in the Premier League this season, is the only player to reach double figures in both. Toney has scored four goals since returning from an eight-month ban over gambling offences in January.
Asked whether they were competing for one spot in the squad, Southgate added: “That is a decision that we have to make. A nine is a specialist position but they have different attributes.
“It would depend a little bit on the injury status in other positions in the squad and also having perhaps players that can play more than one role.
“I think both of them are aware that the opportunity is a big one. But they’re both in good form, they’ve both had time with us.
“Ollie’s been with us more recently, of course, and has done well in the games he’s played. He’s had a fabulous season for his club.
“Ivan, since he’s come back into Brentford’s team, has had the impact we expected him to, so they are two very, very good players.”
England are on a 10-match unbeaten run, winning eight and drawing two, since losing to France in the quarter-finals of the 2022 World Cup.
In contrast, Brazil are on a three-match losing run, having fallen to Uruguay, Colombia and Argentina in World Cup qualifiers. It is their worst run of form in 22 years.
England have only won four of their previous 26 games against Brazil, most recently a 2013 friendly. Their last meeting was a goalless draw in November 2017.
It will be Dorival Jr’s first game as Brazil head coach, having been hired in January.
England have four uncapped players in their squad. Manchester United midfielder Kobbie Mainoo, 18, is one of those, having initially been called up to the under-21s.
Everton defender Jarrad Branthwaite, 21, Newcastle winger Anthony Gordon, 23, and Aston Villa defender Ezri Konsa, 26, are also hoping to make their debuts.
England are without Kane, Henderson, Palmer, Kieran Trippier, Trent Alexander-Arnold, Reece James, Jack Grealish, Luke Shaw and Kalvin Phillips, while Ben White did not want to be considered for selection.
Bukayo Saka was called up but withdrew from the squad on Thursday.
As for Brazil, Gabriel Martinelli, Gabriel Magalhaes, Ederson, Marquinhos and Casemiro have all withdrawn from the squad because of injuries.
Eleven Brazil players could earn their first caps including Wolves midfielder Joao Gomes and Girona winger Savio, who will be playing for Manchester City next season.
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