Understanding the occupational stressors affecting the Centers for Disease Control and Prevention’s (CDC) emergency responders to the coronavirus disease (COVID-19) pandemic is pivotal to understanding how to mitigate future employee stress and burnout during times of prolonged emergency response activations. CDC has experienced challenges with recruiting and retaining a volunteer workforce comprised of CDC employees due to multiple factors, including occupational stressors. This research fills a gap in the public health workforce literature by focusing on a much- overlooked responder population: federal public health emergency response employees. It also fills a gap in the public administration literature related to organizational (occupational) stress factors that lead to stress and burnout during times of prolonged emergency response and crisis. The purpose of this phenomenological research was to explore the lived experiences and perceptions of approximately 1,149 CDC COVID-19 emergency responders regarding the stress and burnout they experienced during their field deployments and Emergency Operations Center (EOC) assignments in support of the CDC’s level 1 emergency response activation that began in January 2020. Data were examined using existing, internal CDC debrief documents, which included first-hand information from responder interviews and their responses to open-ended exit survey questions from March 2020 to July 2021. These debrief documents included recurring themes regarding organizational and other factors affecting responders, including references to stress and burnout, but there has been no holistic review and analysis of what organizational stress factors were more likely to lead to stress and/or burnout — until now. Keywords: Occupational stressors, stress, burnout, emergency response, COVID-19, public health, challenge-hindrance model