Objectives: This study aims to assess health science students’ knowledge and attitude about COVID-19 epidemiology, management, and prevention; and the association of knowledge and attitude with various sociodemographic characteristics. Methods: An online survey was done among 524 undergraduate health science students using a pre-tested questionnaire across 19 health science institutions in Nepal from 30 June to 11 August 2021. All subjects were enrolled in the study after informed consent. Outcomes were Knowledge level, attitude level, and predictors of knowledge level and attitude level. Bivariate analysis was done to determine the association between variables. Results: Of 524 students, 42.9% were male, and 57.1% were female. More than half (54.6%) and the majority (85.1%) participants had good knowledge and attitude, respectively. Approximately three-fifths (59.4%) of the participants were from the B. P. Koirala Institute of Health Sciences (BPKIHS). Students in BPKIHS (odds ratio = 1.774; 95% confidence interval = 1.243–2.533), junior years (odds ratio = 8.892; 95% confidence interval = 5.814–13.599), age less than 23 years (odds ratio = 2.985; 95% confidence interval = 2.089–4.266) were more likely to have good knowledge. Students under 23 years (odds ratio = 24.160; 95% confidence interval: 9.570–60.992) and those in junior years (odds ratio = 4.460; 95% confidence interval = 3.753–5.300) were likely to have a good attitude level. Students in BPKIHS (odds ratio = 0.443; 95% confidence interval = 0.272–0.722) were less likely to have a good attitude. Conclusions: Overall, health science students had adequate knowledge and a good attitude regarding COVID-19. However, students lacked knowledge regarding infectiousness, transmission, post-vaccination observation period, remdesivir use, convalescent plasma therapy, and awake-prone positioning. Knowledge and attitude scores were associated with age, stream, and study institution.