Despite the rapid transmission of and death toll claimed by COVID-19, there is evidence of resistance toward behaviors shown to effectively prevent and slow the spread of the disease, such as mask wearing and social distancing. This study applies psychological reactance theory to examine COVID-19 message factors (i.e., message fatigue, issue importance) that may be linked to nonadherence to CDC recommendations via the experience of reactance. Participants (N = 268) were current U.S. residents over the age of 18 who completed an online survey about their perceptions of COVID-19 messaging in general as well as toward a specific COVID-19 message they recalled. Results of structural equation modeling indicated that perceived freedom threat toward a COVID-19 message was predicted positively by message fatigue and negatively by issue importance. Greater perceived freedom threat was linked to greater reactance, which in turn was associated with lower levels of adherence to hygiene- and social-related COVID-19 preventive behavior. Notably, the negative association between reactance and social-related adherence was stronger than that between reactance and hygiene-related adherence. Implications for the role of reactance in risk and crisis communication as well as for public health messaging during the COVID-19 pandemic are discussed.