On June 25, 2021, this report was posted as an MMWR Early Release on the MMWR website (https://www.cdc.gov/mmwr).Increases in mental health conditions have been documented among the general population and health care workers since the start of the COVID-19 pandemic (1-3). Public health workers might be at similar risk for negative mental health consequences because of the prolonged demand for responding to the pandemic and for implementing an unprecedented vaccination campaign. The extent of mental health conditions among public health workers during the COVID-19 pandemic, however, is uncertain. A 2014 survey estimated that there were nearly 250,000 state and local public health workers in the United States (4). To evaluate mental health conditions among these workers, a nonprobability-based online survey was conducted during March 29-April 16, 2021, to assess symptoms of depression, anxiety, post-traumatic stress disorder (PTSD), and suicidal ideation among public health workers in state, tribal, local, and territorial public health departments. Among 26,174 respondents, 53.0% reported symptoms of at least one mental health condition in the preceding 2 weeks, including depression (32.0%), anxiety (30.3%), PTSD (36.8%), or suicidal ideation (8.4%). The highest prevalence of symptoms of a mental health condition was among respondents aged ≤29 years (range = 13.6%-47.4%) and transgender or nonbinary persons (i.e., those who identified as neither male nor female) of all ages (range = 30.4%-65.5%). Public health workers who reported being unable to take time off from work were more likely to report adverse mental health symptoms. Severity of symptoms increased with increasing weekly work hours and percentage of work time dedicated to COVID-19 response activities. Implementing prevention and control practices that eliminate, reduce, and manage factors that cause or contribute to public health workers' poor mental health might improve mental health outcomes during emergencies.A nonprobability-based convenience sample of public health workers was invited to complete a self-administered, online, anonymous survey during March 29-April 16, 2021. All persons who worked at a state, tribal, local, or territorial health department for any length of time in 2020 were eligible to participate.* * Respondents who did not report working at a state, tribal, local, or territorial public health agency or department in 2020 were excluded from the analysis.