ObjectivesThe sudden outbreak of the novel coronavirus disease (COVID-19) plunged healthcare workers (HCWs) into warfare. This study aimed to determine the prevalence of burnout and the factors associated with it among frontline HCWs fighting COVID-19.MethodsA cross-sectional survey was conducted among frontline HCWs fighting against the COVID-19 in Wuhan, Harbin, and Shenzhen during the period from February 18 to March 4. Finally, HCWs were recruited using cluster sampling, 1,163 HCWs were included in the final analysis. Burnout was measured using a 22-item Maslach Burnout Inventory scale (MBI scale).ResultsOf the participants, 48.6% suffered from burnout, and 21.8% showed a high degree of burnout. Doctors (b = 3.954, P = 0.011) and nurses (b = 3.067, P = 0.042) showed higher emotional exhaustion (EE) than administrators. Participants who worked continuously for more than 8 h a day (b = 3.392, P = 0.000), those who were unable to eat three regular daily meals (b = 2.225, P = 0.008), whose daily water intake was no more than 800 ml (b = 3.007, P = 0.000), who slept for no more than 6 h (b = 1.609, P = 0.036), and who were infected or had colleagues who were infected with COVID-19 (b = 4.182, P = 0.000) experienced much higher levels of EE, while those who could adhere to infection control procedures (b = −5.992, P = 0.000), who were satisfied with their hospital’s infection control measures(b = −3.709, P = 0.001), and who could receive sufficient psychological crisis intervention (b = −1.588, P = 0.039) reported lower levels of EE.ConclusionThe study reveals that burnout is prevalent among frontline HCWs and that the known factors associated with burnout, such as workload, and the factors directly associated with COVID-19, such as having insufficient protection, can affect burnout symptoms in frontline HCWs. Synergized and comprehensive interventions should be targeted at reducing its occurrence among frontline HCWs fighting COVID-19.