The 25-year-old Dutchman had been the overwhelming favourite for the year's race but has fallen victim to flu and a high fever, according to his team Alpecin-Fenix.
Van der Poel has been in stunning form this season and claimed gold in the men's elite race at the 2020 UCI Cyclo-cross World Championships in Switzerland four weeks ago.
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However, a post on the official Alpecin-Fenix Instagram page confirmed that Van der Poel would not be a part of the team's squad in Gent on Saturday.
"Mathieu van der Poel will not be at the start of Omloop Het Nieuwsblad this weekend," the post read.
"Van der Poel has the flu and because of high fever starting Wednesday night, he won't be able to race."
Alpecin-Fenix have named a seven-strong squad for Saturday's classic which comprises of Kristian Sbaragli, Senne Leysen, Otto Vergaerde, Scott Thwaites, Flores De Tier, Petr Vakoc and Dries de Bondt.

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