Under World Cup concussion protocols, player should have 10 days without playing before they can be considered for a return to action. If Maguire had have been concussed, he may have been unavailable for the remainder of the group stage.
Iran had already substituted their goalkeeper Alireza Beiranvand in the first half, forcing a lengthy delay.
But Southgate clarified that the Manchester United defender had been unwell, leading to him being replaced with England up 4-1.
“Harry Maguire felt ill. (He) flagged it before the (first Iran) goal,” Southgate told reporters.
“There was no point carrying on, but other than that, no causes for concern.”
Maguire added on Twitter: “I felt unwell in the second half so came off as a precaution. Looking forward to Friday.”
Maguire’s selection in the England squad was heavily debated having struggled for form in recent times with both club and country.