Former Tour de France winner Andy Schleck pulled out of the race ahead of Tuesday's fourth stage because of an injured knee.
Schleck, 29, the 2010 champion, crashed during Monday's third stage from Cambridge to London after a spectator standing in the road disrupted the peloton.
"Very disappointed to let you know that I will not be able to start," he said on his Twitter feed.
"My knee is too damaged from the crash. This is a huge blow for me."
His Trek team said on Twitter that he would need an operation.
"The ligaments and meniscus in the right knee are too severely damaged from his crash in yesterday's final," said Trek.
"He will travel to Basel now for examination and a possible operation."
Tuesday's fourth stage of the Tour is a 163km run from Le Touquet to Lille.
The news continues a miserable last couple of years for the Luxembourger.
He missed the 2012 Tour after breaking a bone in his lower back in a crash at the Criterium du Dauphine a month beforehand.
Since then he has failed to muster anything like the form that took him to top two finishes in three successive Tours from 2009 to 2011.
Earlier this year he failed to finish any of the three Ardennes Classics and crashed in two of them.
He also had an anonymous ride at last month's Tour de Suisse and suffered the ignominy of being removed as Trek's team leader for the Tour.
He was instead supposed to help brother Frank Schleck and veteran Spaniard Haimar Zubeldia in the high mountain stages.
Schleck's fall from grace these last couple of years has mystified those in the cycling world.
Once thought of as the next great prospect in cycling and a potential multiple Tour winner, his best result in any race since finishing second at the 2011 Tour is a 20th place finish in the Grand Boucle in 2013.
It was thought that Trek's decision to take him out of the spotlight at this Tour would give him the chance to rediscover some of his old form and perhaps win a mountain stage.
He himself insisted before the start of the Tour that he still had a lot to offer the sport.
"I believe I still have a name and I believe I have good capacities and good legs," he said last week.
"I go into the Tour with lower ambitions than the years before; my first objective is to be there to help Frank and Haimar in the climbs.
"There's still a good chance for me to go for a stage. The Tour de France has lots of opportunities."
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