The coronavirus disease 2019 (COVID-19) pandemic causes fear, as its immediate consequences for the public have produced unprecedented challenges for the education and healthcare systems. We aimed to validate the fear of COVID-19 scale (FCoV-19S) and examine the association of its scores with health literacy and health-related behaviors among medical students. A cross-sectional study was conducted from 7 to 29 April 2020 on 5423 students at eight universities across Vietnam, including five universities in the North, one university in the Center, two universities in the South. An online survey questionnaire was used to collect data on participants' characteristics, health literacy, fear of COVID-19 using the FCoV-19S, and health-related behaviors. The results showed that seven items of the FCoV-19S strongly loaded on one component, explained 62.15% of the variance, with good item-scale convergent validity and high internal consistency (Cronbach's alpha = 0.90). Higher health literacy was associated with lower FCoV-19S scores (coefficient, B, -0.06; 95% confidence interval, 95%CI, -0.08, -0.04; < 0.001). Older age or last academic years, being men, and being able to pay for medication were associated with lower FCoV-19S scores. Students with higher FCoV-19S scores more likely kept smoking (odds ratio, OR, 1.11; 95% CI, 1.08, 1.14; < 0.001) or drinking alcohol (OR, 1.04; 95% CI, 1.02, 1.06; < 0.001) at an unchanged or higher level during the pandemic, as compared to students with lower FCoV-19S scores. In conclusion, the FCoV-19S is valid and reliable in screening for fear of COVID-19. Health literacy was found to protect medical students from fear. Smoking and drinking appeared to have a negative impact on fear of COVID-19. Strategic public health approaches are required to reduce fear and promote healthy lifestyles during the pandemic.