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This study explores the association between both individuals' and their partners' COVID-19 exposure and individuals' psychological distress among U.S. adults. This cross-sectional study used data from the 2021 cohort of the Panel Study of Income Dynamics (PSID), a nationally representative probability sample of U.S. adults. Psychological distress was measured using the validated Kessler Psychological Distress Scale (K-6), with scores ≥ 13 indicating clinically significant distress. COVID-19 exposure was defined as either a positive test result or a diagnosis (definite or probable) from a healthcare provider. Multivariate logistic regression examined associations between COVID-19 exposure patterns (self, spousal, both, or neither) and psychological distress, adjusting for demographic, socioeconomic, and health-related confounders. Among 13,809 respondents, 3.87% (n = 534) reported clinically significant psychological distress. Individuals whose spouses had COVID-19 exposure (but they themselves did not) had 1.68 times higher odds of psychological distress compared to those with no self or spousal exposure (95% CI: 1.26–2.23, p < 0.001). Those with both self and spousal exposure had 1.59 times higher odds (95% CI: 1.27–1.99, p < 0.001). However, self-exposure alone without spousal exposure showed no significant association with distress (OR = 1.12, 95% CI: 0.86–1.45, p = 0.39). Spousal COVID-19 exposure is more strongly associated with psychological distress than one's own exposure alone, highlighting the interpersonal nature of pandemic-related mental health burdens. This pattern may reflect the unique psychological challenges of caregiving, including uncertainty about outcomes, a limited sense of control, anticipatory grief, and social isolation. These findings underscore the importance of family-centered approaches to mental health assessment and intervention during global health crises, with mental health services proactively offered to family members of affected individuals.