Bayern, who won four titles this year, lost Sunday’s league game at Hoffenheim 4-1 to suffer their first defeat of 2020.
“Leroy is out. He will most likely be out until and will return after the break for international matches (between October 7-13),” Flick told reporters.
Defender Alaba is doubtful with a muscle problem, with a final decision to be taken on matchday.
The Bavarians almost played through the summer with no real pre-season preparation as they lifted the Champions League in August. They also beat Sevilla last week in the European Super Cup to secure their fourth trophy after also winning the German league and Cup.
“No one has come to me asking for a break,” Flick said. “We know that this season will be a major challenge, not only for us but all teams with many international players.
“For us it is a bit different situation. We had no real pre-season and we had two breaks of two weeks.”
Flick said his team were mentally strong, despite the loss to Hoffenheim which ended their 32-game unbeaten run across all competitions.
“I can only say that the mentality is outstanding,” Flick said. “It could be the case that one player or another is or was a bit tired but when they are on the pitch they give it 100 per cent.”