Benedikt Howedes and Mario Gomez are out of the Germany squad through injury ahead of the second of two consecutive World Cup qualifiers against Kazakhstan on Tuesday.
On Monday, Schalke centre-back Howedes and Bayern striker Gomez were unable to complete a training session because of minor muscle problems.
The German Football Association (DFB) later announced that both had left the team camp after consultation with doctors.
Howedes, 25, played the full 90 minutes as Germany won 3-0 in Astana on Friday, but Gomez missed the match with a pulled muscle.
The Bayern striker's withdrawal brings an end to ongoing discussions about whether Germany should play a centre-forward or a 'false nine'.
It means Dortmund midfielder Mario Gotze, 20, will start in the central role, while versatile Borussia Monchengladbach midfielder Patrick Herrmann could be used as a substitute in the later stages.
Herrmann was called up to the senior squad while on Under-21 duty in Israel and told dfb.de: "I could not believe it at first - I thought it was a joke. It took me two minutes to realise."
However, he stressed that his call-up was no guarantee that he would be involved in the 2014 finals. "I won't go mad just because I have been called up now," he added. "I'm not thinking about Brazil right now."