The 29-year-old midfielder suffered a groin injury and had to be replaced by Bastian Schweinsteiger after only 16 minutes of their tightly contested quarter-final against Italy on Saturday.
However, despite the fact that he will not feature against France in Marseille, coach Joachim Low is hoping that should they progress to the final that Khedira will be available.
"Sami Khedira is definitely not able to play on Thursday," Low said. "We will do everything to see if he can play in a possible final.
"I will probably have to bring new players into the line-up. I trust all of my players, even those who not seen game action."
Khedira is not the only player who will be missing on Thursday as Mats Hummels is suspended and Mario Gomez has been ruled out for the remainder of the tournament with a hamstring injury.
Worringly for Low, one of Khedira's potential replacements, Schweinsteiger, is battling with a knee problem.
"I won't play anyone who is not 100 per cent fit, but I hope Bastian Schweinsteiger is fit and can play," states Low.
"I made the mistake in the past of using a player that was not 100 per cent fit and I will not do it again."