Pep Guardiola potentially faces yet another central defensive selection headache.
Manchester City kick-off a hectic month of fixtures against Manchester United at the Etihad Stadium on Sunday afternoon.
The Premier League Champions are looking to end Erik Ten Hag's sides four game winning streak, and continue their unbeaten start to the campaign this weekend.
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However, Pep Guardiola looks set to be without John Stones, after the defender was forced off midway through the first-half while on international duty on Monday evening.
The 28 year-old, who missed England's defeat to Italy on Friday through suspension, suffered an apparent hamstring injury in the 36th minute against Germany at Wembley Stadium.
Stones was pictured to be visibly upset, as he was replaced by teammate Kyle Walker.
The City centre-back has struggled with injury in the opening weeks of the season, making just six starts for Pep Guardiola's side.
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Against both Borussia Dortmund and most recently against Wolves, the Englishman featured at right-back, amid Kyle Walker's absence through injury.
Manchester City are scheduled to play eight matches next month, with the FIFA World Cup also a matter of weeks away.
Stones' latest injury is a potential huge blow for both the Blues and England.
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Pep Guardiola is expected to welcome Aymeric Laporte back to the first-team after the international break, with the Spain defender having been sidelined since the start of the campaign with a knee injury.
Laporte took to social media earlier this month to announce his return to training.
The Blues also completed a Deadline Day move for Manuel Akanji, who signed from Borussia Dortmund for £15 million amid a host of defensive injury issues for Pep Guardiola's side.
Akanji has enjoyed an impressive start to life at the Etihad Stadium, making three starts at centre-back.
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The Swiss international made his Premier League debut in Manchester City's 3-0 win over Wolves at Molineux.
After the 188th Manchester Derby at the Etihad Stadium this weekend, City face challenging fixtures against both Southampton and Liverpool.
Guardiola's side also face back-to-back matches with FC Copenhagen in the Champions League Group Stages.
Topics: Manchester City, John Stones, England, Premier League