Although research has linked ageism and pain to increased stress in older adults, their influence on stress within the context of pandemics has not been adequately examined. Our objective was to investigate relationships among pain, ageism, and pandemic-related stress in older adults using structural equation modeling (SEM) and mediation analysis. We hypothesized that pain would exert a direct and/or indirect influence on pandemic-related stress, and ageism a direct influence. Data were collected from 486 North American older adults in January 2024. Participants completed measures of pain, ageism, and pandemic-related stress. SEM and mediation analyses yielded evidence suggesting ageism and pain influence pandemic-related stress, although ageism mediated pain’s impact on pandemic-related stress. This study underscores how pain and ageism can impact older adults’ psychological well-being during pandemics. Findings highlight a potential need for public health interventions to address ageism and pain during future waves of COVID-19 or other global health crises.