Both players are nursing injuries as Germany prepare for their World Cup opener and did not train with the squad in Oman on Tuesday.
They will also miss the final warmup match against Oman on Wednesday.
"Thomas Muller has now had a bit of a break but trained well in Munich and will continue to do so here," Flick told a news conference.
"We need a lot of quality in these positions if we are to be successful. I expect Thomas, just like Antonio Rudiger, to start training with the team on matchday minus four for the game against Japan."
In-form midfielder Mario Gotze (30) also sat out training as he recovers from a busy club season at Eintracht Frankfurt.
"Recovery is important. We will see what happens with Mario tomorrow. He's got a lot of matches in his legs already this season so we are very careful about how we go about it," Flick said.
The Germans, hoping to make amends for their shock 2018 World Cup first-round exit, play Japan on November 23 before facing Spain four days later. They wrap up their group matches on December 1 against Costa Rica.
Flick will not be looking at his team to hit top form on Wednesday and may end of resting more players.
"We will see who needs a break, who will play 45 minutes," he said. "But for us it is about bringing all players to the same level to be ready for Japan. That's our plan."
