The Frenchman has endured a difficult season under new management at Cofidis and was not selected for the Tour de France, but he claimed the first Grand Tour victory of his career on stage 6 of the Vuelta, beating Danny van Poppel (LottoNL-Jumbo) and Elia Viviani (Quick-Step Floors).
However, after a disappointing 13th-place finish on stage 10, Bouhanni fell ill and was suffering with stomach problems as he lined up for stage 12 on Wednesday.
"He hadn't slept well and he had stomach pains at the start of the race. He had to go and vomit," said Cofidis DS Jean-Luc Jonrond, according to L'Equipe.
The stage did not turn out to be one an ill rider could drag himself through. As breakaway attempts came and went, the average speed for the first two hours was close to 50km/h, and Bouhanni quickly found himself at the back of the race chasing a lost cause.
After multiple visits to the medical car, he climbed off his bike and into the team car after around 90km of the 207km stage.
"When the race started he was soon dropped but he hoped to get back in," said Jonrond. "However, it was full gas from the gun and, as he was quickly left on his own, it soon became apparent it would be impossible."
Bouhanni will not ride the World Championships later this month but is likely to finish his season in October on home soil, replicating his programme from the past three years, which includes the Tour de Vendée, Paris-Bourges, and Paris-Tours.