BackgroundCountries in the world have been experiencing the ongoing impact and spread of the coronavirus disease (COVID-19) virus pandemic. The health and financial burden of the pandemic has prompted the need for timely and effective vaccination to be considered as the best strategy for controlling disease transmission. However, vaccine acceptability remains an area of concern in developing countries like Ethiopia.ObjectiveTo assess attitude, hesitancy in the COVID-19 vaccine acceptance, and associated factors among health science students at Wolaita Sodo University.MethodsA triangulated mixed-method study was conducted. Quantitative data were entered into SPSS Windows version 25 for analysis, and the qualitative data were transcribed using open code version 4.3. A binary logistic regression model was used to establish the association between dependent and independent variables. Adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to measure the strengths of the association. Thematic approach was used for qualitative data analysis.ResultsA total of 352 students participated in this study. Having family members who were infected with COVID-19, information about COVID-19 vaccine, the need for a vaccine with the level of concern, intention to take COVID-19 vaccine, and academic year were strongly associated with vaccine acceptability. Graduating class and other senior students were about 4 and 2 times more likely to accept vaccination as compared to freshman-year students (AOR = 4.128; 95% CI: 1.351–12.610;P= 0.012) and (AOR = 2.195; 95% CI: 1.182–4.077;Pvalue = 0.013), respectively. Even if 67% of students had a good attitude towards the vaccine, 56% of the students hesitated to take the vaccine.ConclusionThe majority of respondents had a constructive attitude towards the COVID-19 vaccine, and only a few of them were vaccinated against the COVID-19 virus. It is of utmost importance to design an evidence-based strategy to increase the uptake of vaccination for healthcare students and other nonhealth science students in universities.