The two sides last met in September 2017 in a World Cup qualifying match, with the Germans running out 2-1 winners.
Joachim Low will be keen to use this friendly as an opportunity to integrate several new players into the side ahead of the upcoming Nations League matches against Ukraine and Spain, with uncapped players such as Oliver Baumann, Philipp Max, Felix Uduokhai and Bote Baku named in Germany's squad.
Manuel Neuer, Matthias Ginter, Serge Gnabry, Leon Goretzka, Toni Kroos, Leroy Sane and Timo Werner have been ruled out of taking any part in the friendly due to fears of fatigue, which provides opportunities to the aforementioned uncapped players, as well as the likes of Robin Koch, Robin Gosens, Florian Neuhaus, Jonas Hofmann and Luca Waldschmidt, all of whom are still in their infancy in terms of their international careers.
Germany's form has actually been pretty poor by their own high standards since international football resumed in September, drawing four and winning one of their five matches. It leaves them with work to do in order to win Group 4 of the Nations League, with forthcoming opponents Spain one point ahead of them and Ukraine level on points.
A few good performances on Wednesday from some of the fresher faces of the squad could well be the boost Germany and Low need after a testing few years.
Czech Republic manager Jaroslav Silhavy will be eager to put out a much more competitive side than the one he was forced into fielding in the 1-0 defeat at Scotland last month, when the vast majority of his squad were struck by an outbreak of coronavirus.
He is likely to be missing Jan Boril, Ondrej Kudela, Lukas Provod, Filip Nguyen and Michael Rabusic due to the virus, however, with Adam Hlozek, Ondrej Celustka and Patrik Schick ruled out through injury.
Silhavy will be leaning on some of his more experienced players such as West Ham United duo Tomas Soucek and Vladimir Coufal to put in a real shift for him, then, with Nations League fixtures against Israel and Slovakia forthcoming.
With Scotland four points clear at the top of Group 2 with two matches remaining, Silhavy must lead his side to two victories if they are to have any chance of being promoted into Europe's top tier of Nations League groups.
Germany International Friendlies form: LLWDDD
Germany form (all competitions): WDDDWD
Czech Republic International Friendlies form: WLWLLW
Czech Republic form (all competitions): LWLWWL
Bayern Munich midfielder Joshua Kimmich has been ruled out until January after sustaining meniscus damage in his side's 3-2 victory over Borussia Dortmund at the weekend.
With Low missing several other players in the friendly against Czech Republic, he is likely to name a very inexperienced XI in an attempt to blood new faces for the long-term future.
Czech Republic, meanwhile, are also missing several players due to coronavirus and injury, with Schick's absence particularly damaging in attacking areas.
Germany possible starting lineup:
Leno; Henrichs, Koch, Rudiger, Gosens; Neuhaus, Dahoud; Hofmann, Amiri, Brandt; Waldschmidt
Czech Republic possible starting lineup:
Vaclik; Coufal, Hubnik, Celustka, Zeleny; Soucek, Dockal; Malinsky, Darida, Vydra; Krmencik
We say: Germany 2-1 Czech Republic
With both sides missing several players and expected to blood as many newer players as possible ahead of more important Nations League matches, it may not be the most entertaining spectacle for the neutrals.
Germany should have just about enough to overcome a Czech Republic side who are always competitive.