Objective: The COVID-19 outbreak has become a serious public health problem worldwide. The purpose of this study was to use an extended parallel process model (EPPM) to understand factors in COVID-19 prevention behaviors. Methods: This cross-sectional and analytical study was conducted on 1012 participants in Taiwan. A structured questionnaire and an online survey were used to collect data. Results: The EPPM revealed that the severity of the COVID-19 threat perceived by respondents directly affected the arousal of fear in the respondents (β=0.268, t=9.007, p<0.001), but perceived efficacy did not (β=−0.019, t=−0.619, p>0.05); additionally, fear arousal was significantly associated with COVID-19 prevention behaviors (β=0.119, t=4.603, p<0.001). Regarding personal characteristics, self-esteem moderated the relationship between perceived threat and fear arousal. However, the moderating effect of self-esteem was stronger in people with low self-esteem compared to those with high self-esteem (β=0.606, −0.472; t=26.303, −17.694; p<0.001, p<0.001; respectively). The results of this study also indicated that two demographic characteristics (age and gender) affect COVID-19 prevention behaviors. Conclusion: When developing healthcare policies and community interventions for improving COVID-19 prevention behaviors during an outbreak, healthcare administrators should carefully consider the main constructs of the EPPM, particularly personal characteristics (ie, self-esteem) and demographic characteristics (ie, age and gender).