"I have often said that the players are already at their limit," the coach told reporters in Rome on the eve of the match against Italy in Milan on Tuesday.
Bayern Munich CEO Karl-Heinz Rummenigge complained last week about what he said were frequent breaks in club football to accommodate international matches, saying the calendar had become "catastrophic".
Players also regularly complain about the competing pressures on their time created by the scheduling of national and club matches.
Germany beat San Marino 8-0 in a World Cup qualifier on Friday before travelling to Rome to meet Pope Francis and on to Milan.
Several Germany players, including Mats Hummels, Thomas Mueller, Mario Goetze and Joshua Kimmich, will then have to prepare for the biggest game in the German league in recent seasons, with Bayern facing Dortmund on Saturday.
"I am specifically thinking about how to distribute the strain. No player will return to their clubs tired," Loew said.
"I always take care that I rest some key players in November and accommodate the clubs."
He said Bayern's Kimmich will not be playing in central defence as he did against San Marino with Benedikt Hoewedes set to partner Hummels.
"Hoewedes will start, playing next to Hummels," he said. "It is also possible to deploy (newcomer) Yannick Gerhardt from the beginning instead of (left back) Jonas Hector."
Gerhardt is one of three youngsters, who earned their first call-ups, with Serge Gnabry scoring three goals against San Marino and Benjamin Henrichs also starting against the European minnows on Friday.
(Reporting by Karolos Grohmann, editing by Ed Osmond)
