Workload is an essential factor affecting the performance of health care workers (HCWs). High level of mental workload increased their risks of insomnia, anxiety, and depression. This study committed to investigate frontline HCWs' mental workload and analyze its influencing factors during the novel coronavirus disease 2019 (COVID-19) pandemic. A total of 802 frontline HCWs completed the online questionnaires. Their total mental workload score was 69.7 +/- 16.4. Frontline HCWs were satisfied with their performance (4.0 +/- 3.3) and showed a low level of frustration (8.3 +/- 5.7). The most important dimensions of mental workload were "effort" (16.4 +/- 13.7), "physical demand" (15.7 +/- 4.7), and "mental demand" (12.9 +/- 5.2). Frontline nurses and HCWs who have higher education level, longer working years, and higher professional title perceived higher mental workload scores (P < .05). In conclusion, frontline HCWs' mental workload was not high as seen during the COVID-19 pandemic in China. They have made tremendous efforts and dedication to caring for COVID-19 patients. Job-related factors, some of which can be eliminated by proper management skills, increased frontline HCWs mental workload.