Germany striker Miroslav Klose and Arsenal defender Per Mertesacker were on Wednesday ruled out of Friday's friendly against Italy, with Lazio's Klose also sidelined for next week's England game.
"Mirsolav Klose is unavailable for both matches with a very painful shoulder injury. According to initial forecasts he could be out for two to three weeks," Germany manager Joachim Loew reported.
Klose, who shares Germany's all time scoring record of 68 goals with Gerd Mueller, suffered the injury in Lazio's 1-1 Seria A draw with Parma last weekend.
Loew added that he hopes Mertesacker will join up with his squad on Saturday for the England run out next Tuesday.
Loew is hoping that Mertesacker's Arsenal teammate Mesut Ozil, who has been fighting off a viral infection, will be available for the trip to Milan to face Italy followed by the date against Roy Hodgson's England at Wembley.
Germany went through qualifying unbeaten to secure their berth in Brazil for the 2014 World Cup.
The Italy game will be Loew's 100th in charge of Germany.