Although the COVID-19 vaccine is a key intervention against the ongoing COVID-19 pandemic, vaccine hesitancy is a barrier to vaccination coverage, leading to a higher risk of COVID-19-related morbidity and mortality. To reduce vaccine hesitancy, the factors affecting it must be addressed. Based on the determinants of health approach, this study aimed to investigate whether the distribution of determinants of health differed between the vaccine hesitancy group and the vaccine acceptance group and to identify determinants of participants’ hesitancy to receive the COVID-19 vaccine if it was available. This study utilized the 2020 California Health Interview Survey Data collected between May and December 2020. Data were collected using a population-based web and telephone health survey. Data from 21,949 participants in California were included, and 4,183 (23.4 %) showed vaccine hesitancy. The following determinants were positively associated with vaccine hesitancy: female sex, Black and American Indian/Alaskan Native ethnicity, smoking, poverty, U.S.-born citizen, frequent use of social media, food insecurity, and limited healthcare access. Older age, not having severe psychological distress, not having diabetes, and high perceived safety in the neighborhood were negatively associated with COVID-19 vaccine hesitancy. This study also found that higher use of social media potentially threatened vaccine uptake, whereas frequent internet use was negatively associated with vaccine hesitancy. Public health and other relevant service providers should address the determinants of vaccine hesitancy and develop effective strategies and interventions for vaccine-hesitant groups.