The Australian is a perennial favourite at the race, which runs on Saturday, but has been ruled out from making his 11th appearance at La Primavera.
In a statement issued on Tuesday afternoon, Jayco-AlUla wrote: "Michael Matthews has unfortunately tested positive for COVID with light symptoms. Matthews will therefore not be on the start line for this weekend's Milan-San Remo.
"It is a huge disappointment as a season goal and a much-loved race, but health is the priority."
Matthews broke the news of his positive test on Instagram on Monday, posting a photograph of his test result and adding the simple caption "Damn."
Matthews has five top-10 placings and two podiums at the race on his career palmarès, while he finished fourth in the chase group behind solo winner Matej Mohorič at last year's race.
Last year his early season was also disrupted by a COVID-19 infection caught during an altitude training camp in February. He went on to claim stage wins at the Volta a Catalunya and at Mende in the Tour de France, as well as two bronze medals at his home World Championships.
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Matthews has yet to take a race victor in 2023 but did walk away with the green points jersey at the Tour Down Under. He has podiums at the Australian National Championships, stage 1 of the Tour Down Under, and the TTT stage 3 at Paris-Nice to his name.
Jayco-AlUla have yet to confirm their full team for Saturday's race, though veteran racer Zdenek Stybar, who finished seventh in San Remo in 2014, is down to take the start.
Dani Ostanek is Senior News Writer at Cyclingnews, joining in 2017 as a freelance contributor and later being hired full-time. Before joining the team, they had written for numerous major publications in the cycling world, including CyclingWeekly and Rouleur.
Dani has reported from the world's top races, including the Tour de France, Road World Championships, and the spring Classics. They have interviewed many of the sport's biggest stars, including Mathieu van der Poel, Demi Vollering, and Remco Evenepoel. Their favourite races are the Giro d'Italia, Strade Bianche and Paris-Roubaix.
