Cacau, Marc-Andre ter Stegen, Sven Bender and Julian Draxler have all been left out of Germany coach Joachim Low's final 23-man selection for Euro 2012.
Low announced his squad early on Monday, with the quartet flying back to Germany immediately.
The Germany coach, who took a 27-man squad into two training camps in Sardinia and France, will explain his choices on Tuesday when he will be working with his final group in the build-up to their first match of the tournament against Portugal on June 9.
Stuttgart striker Cacau is a surprise exclusion as Low now takes only three forwards with him to Poland and Ukraine - Mario Gomez, Miroslav Klose and Lukas Podolski.
"It was my big goal after the World Cup in South Africa (in 2010) also to be part of Euro 2012 with the Germany national team," Cacau said.
"I knew from the beginning that the competition for the 23 places would be hard and tight.
"I gave it my best shot. Like the younger players, I am also disappointed, but I still feel part of this team and wish them from the bottom of my heart that they play a great European Championships."
Borussia Monchengladbach goalkeeper Ter Stegen made his international debut in Saturday's 5-3 defeat to Switzerland. Despite not passing his first international test, he has vowed to bounce back.
"Of course I am disappointed," he said on the website of the German Football Association (DFB).
"Nevertheless, these days with the national team were an interesting experience for me.
"Despite the defeat to Switzerland, my international debut was an important step in my career and I hope that I will get another chance again soon.
"I would like to wish the team much success at the European Championships."
The exclusions of 19-year-old Draxler and Borussia Dortmund midfielder Sven Bender were less surprising, yet equally upsetting for the two players.
"Of course I would have loved to fly out to Poland and Ukraine," Draxler said.
"But it has not worked out and now I am keeping my fingers crossed that the team wins the title."
Bender, whose twin brother Lars has been included in the 23-man squad, added: "Of course I am sorry to have to return home.
"At the same time, I am pleased for my brother Lars that he will be at the European Championships.
"I hope that the team can realise our dream of winning the title."