BACKGROUND: During the COVID-19 response, nonclinical essential workers usually worked overtime and experienced significant work stress, which subsequently increased their risk of mortality due to cardiovascular diseases, stroke, and pre-existing conditions. Deaths on duty, including deaths due to overwork, during the COVID-19 response were usually reported on web-based platforms for public recognition and solidarity. Although no official statistics are available for these casualties, a list of on-duty deaths has been made publicly available on the web by crowdsourcing. OBJECTIVE: This study aims to understand the trends and characteristics of deaths related to overwork among the frontline nonclinical essential workers participating in nonpharmaceutical interventions during the first wave of COVID-19 in China. METHODS: Based on a web-based crowdsourced list of deaths on duty during the first wave of the COVID-19 response in China, we manually verified all overwork-related death records against the full-text web reports from credible sources. After excluding deaths caused by COVID-19 infection and accidents, a total of 340 deaths related to overwork among nonclinical essential workers were attributed to combatting the COVID-19 crisis. We coded the key characteristics of the deceased workers, including sex, age at death, location, causes of death, date of incidence, date of death, containment duties, working area, and occupation. The temporal and spatial correlations between deaths from overwork and COVID-19 cases in China were also examined using Pearson correlation coefficient. RESULTS: From January 20 to April 26, 2020, at least 340 nonclinical frontline workers in China were reported to have died as a result of overwork while combatting COVID-19. The weekly overwork mortality was positively correlated with weekly COVID-19 cases (r=0.79, P<.001). Two-thirds of deceased workers (230/340, 67.6%) were under 55 years old, and two major causes of deaths related to overwork were cardiovascular diseases (138/340, 40.6%) and cerebrovascular diseases (73/340, 21.5%). Outside of Hubei province, there were almost 2.5 times as many deaths caused by COVID-19-related overwork (308/340, 90.6%) than by COVID-19 itself (n=120). CONCLUSIONS: The high number of deaths related to overwork among nonclinical essential workers at the frontline of the COVID-19 epidemic is alarming. Policies for occupational health protection against work hazards should therefore be prioritized and enforced.