Sylvain Chavanel has been forced to withdraw from Sunday's Paris-Roubaix due to illness.
The 34-year-old IAM Cycling rider would have been one of the main hopes for a home victory in the French one-day Classic.
There has been no French winner of the "Hell of the North" since Frederic Guesdon in 1997.
But the French time-trial champion complained of breathing difficulties following last Sunday's Tour of Flanders, in which he finished 19th and was later diagnosed with "infectious bronchitis and asthma".
His Swiss team have now confirmed he requires rest and adequate treatment before racing again.
Chavanel, whose best Paris-Roubaix finish is eighth in 2009, said: "I'm disappointed to not be taking the start but in my state I'm not able to do so."
He will be replaced by Italian Matteo Pelucchi, who won a stage on the Tirreno-Adriatico stage race last month.