People with asthma may be particularly vulnerable to pandemic-related psychological distress, and research is needed to understand the impact of the coronavirus disease 19 (COVID-19) pandemic on their health and well-being. We sought to study the well-being of people with asthma relative to non-asthmatic controls during the COVID-19 pandemic. We also investigated asthma symptoms and COVID-19-related anxiety as potential mediators of distress. Participants completed self-report measures of psychological functioning, including anxiety, depression, stress, and burnout. Controlling for potential confounds, multiple-regression analyses examined differences in psychological health between people with and without asthma. Mediator analyses investigated the role of asthma symptoms and COVID-19-related anxiety in this relationship. 234 adults (111 with asthma, 123 without) participated in an online survey from July to November 2020. During this time, people with asthma reported higher levels of anxiety, perceived stress, and burnout symptoms compared to controls. Elevations in burnout symptoms were found beyond general anxiety and depression (sr2= .03,p< .001). Reported symptoms typical in both asthma and COVID-19 partially mediated this relationship (Pm= .42,p< .05). People with asthma reported unique psychological challenges during the COVID-19 pandemic including elevated burnout symptoms. Experience of asthma symptoms played a key role in vulnerability to emotional exhaustion. Clinical implications include increased attention to asthma symptom burden within the context of heightened environmental stress and restricted healthcare access.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10865-023-00412-y.