Germany forward Cacau will miss Sunday's World Cup last-16 clash against England in Bloemfontein with an abdominal muscle strain.
Cacau, who scored in the 4-0 win over Australia and started against Ghana, suffered the problem in training.
"The injury will rule him out," said team manager Oliver Bierhoff.
Defender Jerome Boateng is also out and will be replaced by Holger Badstuber at left-back but midfielder Bastian Schweinsteiger has been passed fit.
Miroslav Klose is set to replace Cacau, having served a one-match suspension.
Meanwhile, goalkeeping coach Andreas Koepke said he replaced Joachim Loew at the news conference because the head coach could not get to the Bloemfontein venue in time.
No German player was present at the briefing either - contrary to Fifa regulations - and there was speculation the Germans were angry at not being allowed to train on the Free State Stadium pitch.
Instead they used the facilities at a nearby university complex before the news conference.
But Koepke said: "This is not a protest at all. People were not able to get here on time. We were not able to use the stadium. We had to use another site and tried to be punctual (for the news conference)."
When pressed on what will be viewed as a snub by Loew, Koepke became irritated and added: "We were not able time-wise to get here. We want to be well prepared, that is the reason.
"We were not able to practice on the pitch for logistics reasons. But it is the same for England. We are used to it. We did not practice in the actual stadium the last two times.
"It is not a protest, that's the way it is. There is no point in asking the question again and again."
Fifa said it had taken note of the matter and contacted the German team to remind them of their media duties, but would not take any disciplinary measures.
Meanwhile, Koepke said current number one Manuel Neuer will rise to the challenge of a penalty shoot-out if needed.
"I think it would be great not to have to go to a penalty shoot-out," added Koepke, who saved Gareth Southgate's penalty as Germany beat England in the semi-final at Euro 96.
"If we have to go there, we are prepared. Manuel will of course get the info he needs. But I am not going to give any secrets away.
"We practise penalties but cannot simulate this situation. You have got 120 minutes behind you, the atmosphere is completely different."