Evian - Germany centre-back Antonio Rudiger is out of Euro 2016 after tearing ligaments in his right knee, the German football federation announced.
The AS Roma defender, who is a transfer target for Premier League club Chelsea, was expected to start for the world champions in their opening Group C game against Ukraine on Sunday.
"Antonio Rdiger suffered a torn anterior cruciate ligament in his right knee during a training session for the national team in Evian and is out of Euro 2016 in France," German federation the DFB reported.
He was in contention to make Joachim Loew's line-up as World Cup winner Mats Hummels is not expected to recover in time for the game in Lille as he recovers from a calf tear.
Loew is mulling over whether to call up a replacement into his squad, the federation said.
"The manager... must decide whether to call up an additional player. To summon a player retroactively is allowed under UEFA rules up to the time the team enters the pitch," the DFB explained.
One avenue open to Loew is to deploy Valencia defender Shkodran Mustafi, who figured in his victorious 2014 World Cup squad in Brazil, or Schalke 04's central defender Benedikt Hoewedes, alongside Jerome Boateng.
Loew also has the option of taking a gamble with youth in 21-year-old Bayern Munich back Joshua Kimmich.
With Hummels doubtful for their first run-out it is also unlikely that captain Bastian Schweinsteiger will play the full 90 minutes.
The Manchester United star played the last 23 minutes in last Saturday's 2-0 warm-up win over Hungary in Gelsenkirchen after three months sidelined by a torn medial knee ligament
The Germans, based in Evian, finished top of their Euro 2016 qualifying group, but their defensive frailties were exposed by defeats away to both Poland, who they will again meet in Group C, and the Republic of Ireland.