Grundet DeSantis' modstand mod vaccinekrav, er han af flere blevet stemplet som en vaccineskeptiker (engelsk: ''anti-vaxxer'').<ref name=":16">Mathis, Joel (25. oktober 2021): "[https://theweek.com/politics/1006391/ron-desantis-isnt-just-anti-mandate-hes-anti-vax Ron DeSantis isn't just anti-mandate. He's anti-vax]". ''The Week''. Hentet: 19-12-2021</ref> DeSantis har dog gentagende gange opfordret folk til at lade sig vaccinere, men har dog samtidig fastholdt, at det i sidste ende er et personligt valg og et spørgsmål om personlig frihed.<ref name=":17">Oshin, Olafimihan (21. juli 2021): "[https://thehill.com/homenews/state-watch/564249-desantis-urges-public-to-get-vaccinated-these-shots-are-saving-lives DeSantis urges public to get vaccinated: These shots are 'saving lives]'" ''The Hill''. Hentet 19-12-2021</ref><ref name=":18">Downey, Renzo (18. november 2021): "[https://floridapolitics.com/archives/474484-gov-desantis-signs-vaccine-mandate-ban-freedom-policies-in-covid-19-package/ DeSantis frames his opposition to the vaccine mandates as a defense of personal freedoms.]". ''Florida Politics''. Hentet 19-12-2021</ref>
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