Germany captain Manuel Neuer and forward Thomas Muller are both injured and ruled out of Thursday's World Cup qualifier against minnow Liechtenstein.
Arsenal goalkeeper Bernd Leno will deputise for Neuer, who sat out training all week with an ankle knock.
Coach Hansi Flick is hopeful he will be fit for for their next qualifier against Armenia in Stuttgart.
"We assume that 'Manu' will be back for Sunday," Flick said on Wednesday.
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Neuer's Bayern Munich team-mate Muller is suffering an adductor injury and misses all three Group J games against Liechtenstein, Armenia and Iceland next Wednesday.
"Thomas has gone home, the injury made it not possible for him to play in the games," added Flick.
"The risk was too great, so it made sense to send him home.
"We have enough players to replace him."
Borussia Dortmund captain Marco Reus or Chelsea forward Kai Havertz could deputise.
Without Neuer, 35, and Muller, 31, Germany lose a decade of experience as the pair have over 200 international appearances between them.
Germany has ground to make up in its qualifying group as it sits third, two points behind leader Armenia.
In Neuer's absence, Flick has still to decide who wears the captain's armband against Liechtenstein.
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"I asked myself under the shower who will be captain," said Flick.
"I'll have a think about it, we have a few options and will clarify it internally."
This will be his first international as Germany head coach.
After defeat to England in the last 16 of Euro 2020, Joachim Low stepped down after 15 years in charge and has been replaced by his assistant coach when Germany won the 2014 World Cup.
"I'm looking forward to my first international game and the responsibility for the nation," added Flick, who wants the same "intensity" from his team as he has seen in training.
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