Roma defender Antonio Rudiger will undergo surgery on Saturday after tearing his anterior cruciate ligament.
Rudiger was set to feature for Germany at Euro 2016 - with Mats Hummels battling a calf problem - but the 23-year-old suffered heartbreak on Tuesday.
In the world champion's first training session in France ahead of the Euros, Rudiger collapsed to the ground in clear discomfort after making a tackle.
Germany coach Joachim Low has added Bayer Leverkusen defender Jonathan Tah as Rudiger's replacement.
"Antonio Rudiger has today undergone an MRI scan which confirmed the rupture of his anterior cruciate ligament," a Roma statement said.
"His prognosis will be determined after he undergoes surgery [on Saturday]."
Drawn in Group C, Germany open their campaign against Ukraine on Sunday, before facing Poland (June 16) and Northern Ireland (June 21).