Die Mannschaft - who sit at the top of League A Group 3 with four points from their opening two games - have already lost five players to injury this month, including Arsenal's Kai Havertz and Bayern Munich's Jamal Musiala.
Benjamin Henrichs, David Raum and Robin Koch have also withdrawn from the October squad, while other key names such as Niclas Fullkrug and Marc-Andre ter Stegen are absent from the ranks this month.
With neither Ter Stegen nor the retired Manuel Neuer available, 34-year-old Oliver Baumann is expected to make his senior debut in goal, where he ought to be offered protection by a solid backline.
Indeed, all of Antonio Rudiger, Joshua Kimmich, Jonathan Tah and Maximilian Mittelstadt are fit and firing, as are Robert Andrich and Pascal Gross, who could form the two-man midfield pairing.
Should Nagelsmann opt for another 4-2-2-2 setup, Florian Wirtz will no doubt occupy one of the advanced positions, and Serge Gnabry could hold off the threat of Kevin Schade to start on the left.
In the absence of Havertz and Fullkrug, Deniz Undav is Germany's chief attacking threat, and the one-time Brighton & Hove Albion man may be joined by the uncapped Jonathan Burkardt, who boasts five goals from his first six Bundesliga appearances of the season for Mainz 05.
Germany possible starting lineup:
Baumann; Kimmich, Tah, Rudiger, Mittelstadt; Wirtz, Andrich, Gross, Gnabry; Undav, Burkardt