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Werner limped off early in Leipzig's 4-0 win in the UEFA Champions League on Thursday (AEDT), and the club have since confirmed their star forward will miss the remainder of the year.
"Timo Werner suffered an ankle injury last night in the win over Shakhtar Donetsk," a club statement read.
"Scans today in Leipzig showed that he has unfortunately torn the syndesmosis ligament in his left ankle and will therefore be out for the rest of 2022."
The 26-year-old's injury is a blow to both Germany and Leipzig, for whom he had rediscovered his finishing touch following two disappointing seasons at Chelsea.
Known for his pace and potency, Werner produced nine goals and four assists through 16 games this season and figured to lead the line for Germany in Qatar.
With 24 goals in 55 outings for Die Mannschaft, Hansi Flick admitted Werner's absence would be "a big loss for the team".
"It's very sad news," Flick said. "I feel really sorry for Timo that he will miss a World Cup that he was determined to play at.
"Above all though, his absence is a big loss for the team. We all wish him a speedy recovery!"
Kai Havertz will likely lead Germany's line in Werner's absence, in a role akin to the one he's had to learn at Chelsea.
