Midfielder Kroos, 20, has helped Bayer Leverkusen to the top of the Bundesliga with an unbeaten run of 23 matches while Mueller, also 20, has been inspirational for Bayern who recently won 13 games in a row.
"Both have produced some very good performances in the Bundesliga in the last few months and deserve a chance," said coach Joachim Low on the German federation website.
The match is Germany's last friendly before Low, recently involved in a controversy over the extension of his contract after the World Cup, names his squad for South Africa.
Cacau made four appearances for Germany last year, three of them as a substitute, but was not included in the squad for their most recent match, a 2-2 draw against Ivory Coast in November.
He scored four goals in Stuttgart's 5-1 win at Cologne at the weekend and was also on target in Tuesday's 1-1 draw at home to Barcelona in the Champions League.
As he promised earlier this week, Low kept faith with goalkeepers Rene Adler and Manuel Neuer despite much-criticised performances from both in the Bundesliga the previous weekend.
Tim Wiese, who was also due to be included, was left out because of a hamstring injury.
Goalkeepers: Rene Adler (Bayer Leverkusen), Manuel Neuer (Schalke 04)
Defenders: Jerome Boateng (Hamburg SV), Arne Friedrich (Hertha Berlin), Philipp Lahm (Bayern Munich), Per Mertesacker (Werder Bremen), Marcel Schaefer (VfL Wolfsburg), Serdar Tasci (VfB Stuttgart)
Midfielders: Michael Ballack (Chelsea), Christian Gentner (VfL Wolfsburg), Thomas Hitzlsperger (Lazio), Aaron Hunt (Werder Bremen), Marcell Jansen (Hamburg SV), Sami Khedira (VfB Stuttgart), Toni Kroos (Bayern Leverkusen), Marko Marin (Werder Bremen), Thomas Mueller (Bayern Munich), Mesut Ozil (Werder Bremen), Bastian Schweinsteiger (Bayern Munich), Christian Traesch (VfB Stuttgart), Piotr Trochowski (Hamburg SV)
Forwards: Cacau (VfB Stuttgart), Mario Gomez (Bayern Munich), Stefan Kiessling (Bayer Leverkusen), Miroslav Klose (Bayern Munich), Lukas Podolski (Cologne)
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