Goalkeeper Manuel Neuer and midfielder Leon Goretzka will miss Germany's Nations League fixtures against Hungary and England after testing positive for Covid.
The Bayern Munich pair have left the team camp in Frankfurt and are isolating after returning positive tests on Wednesday morning.
Julian Brandt has also left the squad with flu-like symptoms, though has tested negative for the coronavirus.
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Hoffenheim goalkeeper Oliver Baumann has been called up to Hansi Flick's squad to replace Neuer, who had been again set to captain his country, while Maximilian Arnold, who has three senior caps, will provide midfield cover.
The players were tested after a close personal contact of the pair returned a positive of their own, and recent contacts of both Neuer and Goretzka will now be tested daily.
Flick's side sit second in Nations League Group A3, a point and a place behind Hungary, who they host in Leipzig on Friday night.
Germany then visit Wembley to face England on Monday.
Flick's squad for the two matches includes the uncapped Armel Bella-Kotchap, who has made an eye-catching start to life in the Premier League after a summer move to Southampton.
"Armel Bella-Kotchap has developed very well," Flick said after selecting the 20-year-old centre-half. "[I wanted to] get a first-hand impression.
"It is important for us to know what will come next. He has been defending well for Southampton and in the Premier League, which says a lot."
Bella-Kotchap's inclusion appears a blow to Mats Hummels' chances of making the Germany World Cup squad.
The veteran central defender has been back to somewhere near his best for Borussia Dortmund, though, and Flick insists that the door is not shut on a possible return for the 33-year-old.
“Everyone still has a chance to jump on the World Cup train," Flick said.
“BVB delivered a great performance and defended superbly for 80 minutes [against Manchester City last week]. I especially liked Mats Hummels. He is in very good form and looks absolutely fit.”

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Germany will be in Group E alongside Japan, Costa Rica and Spain in Qatar.
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