ABSTRACT This study examined the roles of normative and epistemic factors in influencing individuals’ reluctance to be vaccinated during the COVID-19 pandemic. Individuals’ ethical orientations (IEO; teleology vs. deontology) were introduced as normative characteristics, while COVID-19 vaccine conspiracy beliefs and vaccine knowledge were addressed as issue-specific epistemic factors. We conducted two online surveys to investigate each of these three factors’ influences on the level of Americans’ reluctance to receive COVID-19 vaccines. Combinations of these factors that predict COVID-19 vaccination hesitancy levels were also explored to provide integrated perspectives in the specific vaccination context. Our findings demonstrated the positive association between IEO and reluctance to receive COVID-19 vaccines. Significant interactions between 1) COVID-19 vaccine conspiracy beliefs and IEO and 2) conspiracy beliefs and vaccine knowledge were also identified. Implications, limitations, and suggestions for future study were addressed.