The 26-year-old defender was forced off at half-time in City's 3-1 Premier League loss at Nottingham Forest over the weekend and Enzo Maresca confirmed the player himself had requested to be substituted.
Guehi has since undergone scans on a hip issue and the results have ruled him out of England duty this month.
Thomas Tuchel's team wrap up their UEFA Nations League campaign with matches against Croatia (November 12th and Spain (November 15th) and the Three Lions boss will now have to reshuffle his backline with Dan Burn added as a replacement.
The former Crystal Palace captain started in all but one of England's games at the 2026 FIFA World Cup this summer and all four Nations League fixtures in September and October.
Guehi could be the first of several squad withdrawals in the coming days amid injury and overload concerns on Declan Rice and Dominic Calvert-Lewin.