Although the mental health consequences of individual COVID-19 stressors (e.g., bereavement, job loss, or financial strain) have been well-documented, little is known about the cumulative toll of multiple pandemic stressors. Using national data from the Crime, Health, and Politics Survey (May–June 2021), we test whether the accumulation of pandemic stressors is associated with greater psychological distress. We also consider whether this association is moderated by psychosocial resources (i.e., mastery, self-esteem, and social support). Our findings suggest that individuals who report three or more pandemic stressors tend to exhibit greater psychological distress than those who report fewer pandemic stressors or no pandemic stressors. While mastery offsets the impact of pandemic stressors at higher levels of stress exposure (i.e., two or more COVID-19 stressors), social support and self-esteem played a stress-buffering role to a point, but became ineffective at the highest levels of pandemic stress. The current study provides new insights into the pandemic stress process by conceptualizing and operationalizing the cumulative impact of COVID-19 stressors. We also confirm the continued significance of traditional coping resources in the context of novel pandemic stressors.