Joachim Low revealed Shkodran Mustafi tore his thigh muscle in Germany's 5-1 World Cup qualifying win over Azerbaijan on Sunday.
The Arsenal defender pulled up clutching his hamstring in the build-up to Azerbaijan's equaliser in the first half and was replaced by Matthias Ginter.
After the match, Low confirmed the 25-year-old had suffered a tear and could be set for a prolonged spell on the sidelines.
"With Mustafi it seems that it is some muscle tear or some muscle fibre tear," Low said. "In any case it could force him to a longer break."
Niklas Sule was also withdrawn in the first half with an injury, but the game will be remembered for another display of fluent attacking football that wrapped up Germany's World Cup qualifying campaign with a 100 per cent record.
A brace from Leon Goretzka, goals from Sandro Wagner and Emre Can and an own goal from Badavi Huseynov secured all three points and ensured that Germany are the only team in Europe to qualify having won all 10 of their group games.
Low, however, is refusing to get carried away and knows his side will face tougher tests as they bid to win a second consecutive World Cup in Russia next year.
"One makes a mistake if one sets this qualification as a benchmark," he added.
"Sure, it was good, it was a clear achievement, but at the World Cup you come up against quite different calibres of sides.
"There is still a lot to do. I want to achieve something very great in a few months. It will be hard to become world champions twice."