Germany defender Antonio Rudiger will miss Euro 2016 after tearing the anterior cruciate ligament in his right knee in training on Tuesday.
The Roma centre-half was training with teammates in France when he ruptured his ACL, the DFB announced on Tuesday evening.
Rudiger played the full 90 minutes in each of Germany's past five matches and had been expected to line up in the starting formation once again for his country's opening game of the tournament against Ukraine on June 12.
"The Germany international has been ruled out of the European Championship after rupturing the anterior cruciate ligament in his right knee during Die Mannschaft's first training session in Evian," read a statement on the governing body's official website.
"This was confirmed by an examination carried out by Dr. Hans-Wilhelm Muller-Wohlfahrt and the medical team.
"Joachim Low and the rest of the management team will now make a decision on whether they will call up a replacement, with UEFA regulations allowing them to do so until the first match day."
- Bayern & Germany (@iMiaSanMia) June 7, 2016
Rudiger, 23, made his professional debut for Stuttgart in January 2012 and was handed the first of his 11 caps for his country against Poland in a goalless draw 28 months later.
He joined Roma on loan last summer, making 30 appearances for the Serie A outfit before signing a permanent four-year deal in the Italian capital last week.
He was set to deputise for centre-back Mats Hummels, with the Bayern Munich defender recovering from a calf injury picked up in mid-May.
His withdrawal leaves Germany with Shkodran Mustafi, Jonas Hector, Benedikt Howedes, Mats Hummels, Jerome Boateng and Joshua Kimmich as defensive options in the squad.