Maguire sat down on the pitch at the Khalifa International Stadium just after the hour and was immediately attended to by the England medical team.
Physios could be seen performing a concussion test, which is the protocol in such scenarios.
It was not entirely clear how Maguire sustained the injury. He was treated for several minutes before being carried off the field.
The 29-year-old man was clearly very dazed as he chatted with the staff. He then exchanged words with his replacement, Eric Dier, before heading straight for the tunnel.
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The 48-cap ace struck back at critics of his World Cup inclusion with his performance. However, he could now miss England’s game against the United States on Friday after being substituted with a concussion.
Under FIFA guidelines, any player who sustains a concussion must be re-evaluated within 72 hours of leaving the field. That could leave Maguire facing one race to get ready for the second Group B clash.
That differs from Premier League guidelines, which insist players must not take part in sporting activities for at least six days.
England continued to sail past Iran without Maguire.
They led 4-1 before his injury, with Jude Bellingham, Raheem Sterling scoring and Bukayo Saka scoring a brace.
Mehdi Tahremi recovered a goal for the Asian side, before Maguire’s Man Utd teammate Marcus Rashford restored the four-goal lead after coming on as a substitute.
Jack Grealish scored a sixth goal to round off an excellent start to the 2022 World Cup for Gareth Southgate’s side.
Tahremi scored a late penalty for Iran after John Stones was penalized for removing his shirt.
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