There is a public health need to understand mental health vulnerabilities to COVID-19 pandemic-related stressors and promote resilience among high-risk populations with preexisting psychiatric conditions. Recent cross-sectional studies suggest increases in mental health distress (e.g., depression and anxiety) during the pandemic. The present study expands upon these emerging findings using longitudinal latent modeling and hierarchical linear regressions. Consistent with the developmental psychopathology literature on resilience, we distinguished between promotive or risk (i.e., main effect), and protective or vulnerability (i.e., moderation) effects on mental health during the pandemic. At a large medical center, 398 veterans receiving outpatient mental health care provided prepandemic (Time 1) and during pandemic (Time 2) assessments of mental and physical health-related distress. Additional Time 2 questionnaires assessed pandemic-related stressors and positive behavioral adaptations in the summer of 2020. As expected, total stressor scores predicted longitudinal worsening of self-reported mental (β = -.205) and physical health (β = -.217). Positive behavioral adaptations enacted during the pandemic moderated and protected against stressor effects on mental health (β = .160). In addition, the presence of substance use disorders moderated and conferred vulnerability to stressor effects on physical health (β = -.158). Thus, higher COVID-19 pandemic stressor exposure may have exacerbated mental and physical health distress among veterans with common forms of psychopathology. Nevertheless, behavioral activation, purposeful maintenance of social connections, and focused treatment for substance misuse may be important intervention targets for reducing the longitudinal impact of pandemic stressors and enhancing resilience among people with mental illness. (PsycInfo Database Record (c) 2023 APA, all rights reserved).