Captain Manuel Neuer and winger Julian Brandt are the latest German players to withdraw from Friday's World Cup qualifier with San Marino. The German football association confirmed the pair's absence on Wednesday.
Neuer, 30, pulled out of the squad shortly before Germany's flight from Frankfurt to Rimini because he felt unwell. He will also miss next Tuesday's friendly against Italy in Milan.
Barcelona's Marc Andre ter-Stegen and Bayer Leverkusen's Bernd Leno are the contenders to take the Bayern Munich keeper's place between the sticks.
Leno's Leverkusen teammate, Julian Brandt, also stayed at home, with reports suggesting he is suffering from an intestinal disorder.
Neuer is the latest first-choice star to drop out after Real Madrid's Toni Kroos, who has a fractured foot, and Bayern teammate Jerome Boateng, who is out with an injured knee and groin.
With Mesut Özil rested and Julian Draxler injured, the world champions are likely to be without almost half of their first-choice 11, though they are unlikely to be too troubled by the tiny microstate on Friday - San Marino have won just one game in their history.
Despite the odds being heavily stacked in their favor, Germany coach Joachim Löw expects nothing less than total focus on Friday.
"We will treat the last qualification game of the year exactly the same as the three previous games," he said after Germany's wins over Norway, the Czech Republic and Northern Ireland in the last two months.
"We don't want to be arrogant in San Marino and will treat this with high levels of concentration and seriousness."
The latest withdrawals are likely to mean a chance to impress for a number of fringe players, possibly including Yannick Gerhardt of Wolfsburg, Werder Bremen's Serge Gnabry and Benjamin Henrichs of Leverkusen who were all called up to the squad for the first time.