Joachim Low has trimmed his squad and there is no place for the Borussia Dortmund star, with Karim Bellarabi, Julian Brandt and Sebastian Rudy also omitted.
Low confirmed that Reus is struggling physically telling a press conference: "It has been a bitter decision for us and for him [Reus], and a disappointment for us all.
"Marco Reus in a good shape and healthy and fit -that would have been a tremendous asset to our team.
"I thank the four players, they presented themselves very well in training, they gave everything and I hope they put away this disappointment well, it is not a decision against four players but a decision for 23 players."
Germany squad in full:
Defenders: Jerome Boateng (Bayern Munich), Emre Can (Liverpool), Jonas Hector (Cologne), Benedikt Howedes (Schalke), Mats Hummels (Borussia Dortmund), Shkodran Mustafi (Valencia), Antonio Rudiger (Roma)
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)