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Background: The health belief model suggests that individuals' beliefs affect behaviors associated with health. This study examined whether Ohioans' pre-existing medical health diagnoses affected their belief about personal health risk and their compliance with social distancing during the coronavirus disease 2019 (COVID-19) pandemic. Prior research examining physical and mental diagnoses and social distancing compliance is nearly nonexistent. We examined whether physical and mental health diagnoses influenced individuals' beliefs that their health is at risk and their adherence with social distancing guidelines. Methods: The study used longitudinal cohort data from the Toledo Adolescent Relationships Study (TARS) (n = 790), which surveyed Ohioans prior to and during the COVID-19 pandemic. Dependent variables included belief that an individual's own health was at risk and social distancing compliance. Independent variables included physical and mental health diagnoses, pandemic-related factors (fear of COVID-19, political beliefs about the pandemic, friends social distance, family social distance, COVID-19 exposure), and sociodemographic variables (age, gender, race/ethnicity, educational level). Results: Individuals who had a pre-existing physical health diagnosis were more likely to believe that their personal health was at risk during the pandemic but were not more likely to comply with social distancing guidelines. In contrast, individuals who had a pre-existing mental health diagnosis were more compliant with social distancing guidelines but were not more likely to believe their personal health was at risk. Individuals who expressed greater fear of COVID-19 believed their health is more at risk than those who expressed lower levels of fear. Conclusion: Health considerations are important to account for in assessments of responses to the pandemic, beliefs about personal health risk, and social distancing behavior. Additional research is needed to understand the divergence in the findings regarding physical health, beliefs about personal health risk, and social distancing compliance. Further, research is needed to understand how mental health issues impact decision-making related to social distancing compliance.