Sami Khedira has been ruled out of Germany's Euro 2016 semifinal against France on Thursday, while captain Bastian Schweinsteiger is facing a race against time to return to full fitness.
On Saturday, Germany beat Italy in a dramatic penalty shootout to advance to their sixth consecutive semifinal at a major tournament.
However, the win came at a cost and the Nationalmannschaft are set to make major changes for their semifinal with hosts France.
At the weekend, attacker Mario Gomez was ruled out for the remainder of the tournament, and Germany coach Joachim Low has also confirmed that midfielder Khedira will also not take part in the match against France.
Schweinsteiger is also a major injury doubt, while defender Mats Hummels will sit out through suspension.
"The Italy match and the 120 minutes left their traces," Low told a news conference at Germany's tournament base in Evian. "Gomez will miss the rest of the tournament, and Khedira will also not be able to play on Thursday. We will do all we can that he can play in an eventual final."
Against Italy, Khedira had to be withdrawn with a groin problem after only 15 minutes, and he was replaced by Schweinsteiger, who himself took a knock to the knee only minutes after coming off the bench.
Although the Germany captain battled through until the very end, he now faces an uphill task to take part in the semifinal.
"Schweinsteiger picked up a minor injury, his situation did not improve after the match. We will have to wait and see. Hummels is suspended," Low said, later adding that the Manchester United midfielder will only allowed to take to the pitch if declared fully fit.
"Players with minor injuries will definitely not play. That's clear. I hope that he gets fit in time, because Bastian can give our team a lot. But I will definitely not play someone of whom I am not convinced that he can go 90 or 120 minutes. I've done that in the past, and I won't make the same twice. But I won't go into details who and when that was."
With up to four players out for Thursday, Low said that Germany "will have to make changes and find solutions."
The vacant position next to Toni Kroos in holding midfield could be Germany's most pressing issue against France.
While Low ruled out playing Joshua Kimmich there, if Schweinsteiger were to miss the match, the coach would have to make a decision between Liverpool's Emre Can and Dortmund's Julian Weigl -- neither has played a minute at the Euros so far.
"I will need to make changes, but I trust all players, even those who have yet to make an appearance," Low said. "They are at a very, very high level in training and in a good physical state."
Talking about the decision between Can and Weigl, Low praised both and left his answer open.
"They are different player types. Can has played on many positions for us. He is forceful, physically strong, and has a good technique. Can would be a great fit and help us," Low said.
"Weigl does things differently, he closes the passing paths with his running, is incredibly strong with the ball. Can is also very, very good with the ball. The era of the enforcer in midfield has ended. Let's see what the decision will be."