Cyclingnews will have live coverage of Milan-San Remo from 8am GMT on Saturday, March 19.
"It's disappointing for me to miss one of the biggest classics of the season," Dumoulin said in a team statement.
"It started at Paris-Nice. From Saturday to Sunday I had a sore throat and didn't feel completely well during Sunday's closing stage and once home it continued to get worse. It is a pity that I can't start Milan-San Remo but I need to accept it. I hope I will be fit in time for Catalunya and in the coming days we will know more."
Dumoulin will be replaced by teammate Bert de Debacker but the Dutchman’s absence comes as a major blow after they were already set to ride without defending champion John Degenkolb – the German still recovering from being hit by a car earlier in the year.
"Tom has the flu and with only two days to Milan-San Remo, we decided it won't be possible for him to race. He is recovering at home and we will monitor his progress closely. We expect Catalunya to be possible but we have to wait and take it day by day,” said team doctor Anko Boelens.
Giant Alpecin coach, Marc Reef, confirmed that the team’s tactics for Milan-San Remo would change as a result of their late line-up alteration.
"It's very unfortunate that Tom won't be starting on Saturday since he is considered as one of our riders capable of handling the tough finale at Milan-San Remo. Our plan will change slightly, which means that we will race more opportunistically and the aim is still to bring Simon [Geschke] to the finale as fresh as possible.".