Objectives This study was conducted to identify the level of mental health and burnout of medical staff at hospitals and public health centers, which responded to the coronavirus disease 2019 (COVID-19) in South Korea and to suggest appropriate management plans. Methods The mental health and burnout levels of medical staff responding to COVID-19 were evaluated through an online survey conducted during the period July 1–14, 2021. To analyze the mental health status of the participants according to their demographic characteristics, the chisquare test, t-test, and an analysis of variance were conducted, followed by Scheffe post-hoc tests for pairwise comparisons. Results A total of 773 participants were included in the study. An analysis of the clinically significant symptoms of the group showed that 29.5% had posttraumatic stress symptoms, 30.6% had depression, 15.8% had anxiety, 39.8% had somatic symptoms, and 4.5% were seen to be at risk of suicide. The average scores for burnout were as follows: 3.55±1.75 for emotional exhaustion, 2.68±1.73 for depersonalization, and 3.89±1.40 for personal accomplishment. Mental health problems and burnout were found to be high in women, those in the 20–39-year age bracket, those with less than 5 years of work experience, and public health center workers. Conclusion The medical staff responding to COVID-19 were observed to experience high levels of mental health and burnout problems. Work-related characteristics, such as younger age, lower work experience, and employment at a public health center, may have a negative impact on mental health and cause burnout. Therefore, individualized and systemic support for mental health and to prevent the burnout of medical staff responding to cases of COVID-19 is needed.