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Background: During the coronavirus disease (COVID-19) pandemic, social media platforms have become active sites for the dissemination of conspiracy theories that provide alternative explanations of the cause of the pandemic, such as secret plots by powerful and malicious groups. However, the association of individuals' beliefs in conspiracy theories about COVID-19 with mental health and well-being issues has not been investigated. This association creates an assessable channel to identify and provide assistance to people with mental health and well-being issues during the pandemic., Objective: Our aim was to provide the first evidence that belief in conspiracy theories regarding the COVID-19 pandemic is a predictor of the mental health and well-being of health care workers., Methods: We conducted a survey of 252 health care workers in Ecuador from April 10 to May 2, 2020. We analyzed the data regarding distress and anxiety caseness with logistic regression and the data regarding life and job satisfaction with linear regression., Results: Among the 252 sampled health care workers in Ecuador, 61 (24.2%) believed that the virus was developed intentionally in a lab; 82 (32.5%) experienced psychological distress, and 71 (28.2%) had anxiety disorder. Compared to health care workers who were not sure where the virus originated, those who believed the virus was developed intentionally in a lab were more likely to report psychological distress and anxiety disorder and to have lower levels of job satisfaction and life satisfaction., Conclusions: This paper identifies belief in COVID-19 conspiracy theories as an important predictor of distress, anxiety, and job and life satisfaction among health care workers. This finding will enable mental health services to better target and provide help to mentally vulnerable health care workers during the ongoing COVID-19 pandemic., (©Xi Chen, Stephen X Zhang, Asghar Afshar Jahanshahi, Aldo Alvarez-Risco, Huiyang Dai, Jizhen Li, Verónica García Ibarra. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 21.07.2020.)