The Dutchman, who won the Giro d'Italia in May and the time trial world title last month, was due to race the Italian Monument as his final outing of what has been a hugely successful campaign. However, after failing to finish Milano-Torino on Thursday, he woke up feeling unwell on Friday.
"Tom has woken up with flu and a sore throat and we have made the decision to take him out of the race," said Sunweb physician Anko Boelens. "He will need a few days of rest to be able to fully recover."
Dumoulin finished fifth at Strade Bianche earlier this year and was set to be a co-leader for Sunweb at Saturday's Il Lombardia, alongside Warren Barguil. Laurens Ten Dam has been drafted in as a replacement.
"With Tom not starting tomorrow we miss one of our leaders so we have taken another look at our tactical plan for the race. Although with such a strong line-up we are confident that we will end our time in Italy on a high," said directeur sportif, Aike Visbeek.
"Warren remains our leader for the race and both Wilco [Kelderman] and Sam [Oomen] will now stay focused on supporting him for the final. After a strong ride at yesterday's Milano-Torino, we would also like to have Chris [Hamilton] together with Laurens [Ten Dam] to help positioning the guys in the front. After doing a course recon we have seen that this is a really demanding course and we look forward to a challenging day tomorrow."
Dumoulin's season, therefore, ends with a DNF at Milano-Torino, though nothing could take the gloss of what he has achieved this year. He came of age as a Grand Tour rider to win the Giro d'Italia in May, and he went on to win the BinckBank Tour in August followed by the individual and team time trial double at the World Championships.