Reus, who turned 27 on Tuesday, has been cut from the squad due to concerns over his fitness, according to head coach Joachim Low.
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Euro 2016: Marco Reus out of Germany squad
Borussia Dortmund forward Marco Reus has been left out of Germany's final squad for Euro 2016.
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"He can only just about run at the moment," Low said of Reus, who also missed the World Cup two years ago due to injury.
"It's a bitter decision, for us and for him. He would have been an asset."
Juventus midfielder Sami Khedira, who earned a place in the final 23, added: "It's never easy for the team when players are cut from the squad. Marco took the disappointing news in a very composed manner."
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Hoffenheim midfielder Sebastian Rudy, as well as Bayer Leverkusen attacking midfielders Karim Bellarabi and Julian Brandt, have also been omitted.
Captain Bastian Schweinsteiger is included despite concerns over a knee injury that kept him sidelined for much of the second half of Manchester United's season. Youngsters Julian Weigl and Joshua Kimmich are also in the squad.
Germany squad in full:
Goalkeepers: Manuel Neuer (Bayern Munich), Bernd Leno (Bayer Leverkusen), Marc-Andre ter Stegen (Barcelona)
Defenders: Jerome Boateng (Bayern Munich), Emre Can (Liverpool), Jonas Hector (Cologne), Benedikt Howedes (Schalke), Mats Hummels (Borussia Dortmund), Shkodran Mustafi (Valencia), Antonio Rudiger (Roma)
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Midfielders: Julian Draxler (Wolfsburg), Mario Gotze (Bayern Munich), Sami Khedira (Juventus), Joshua Kimmich (Bayern Munich), Toni Kroos (Real Madrid), Mesut Ozil (Arsenal), Leroy Sane (Schalke), Bastian Schweinsteiger (Manchester United), Julian Weigl (Borussia Dortmund)
Forwards: Mario Gomez (Besiktas), Thomas Muller (Bayern Munich), Lukas Podolski (Galatasaray), Andre Schurrle (Wolfsburg)
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