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Abstract Background Cross-sectional studies have found that the coronavirus disease 2019 (COVID-19) pandemic has negatively affected population-level mental health. Longitudinal studies are necessary to examine trajectories of change in mental health over time and identify sociodemographic groups at risk for persistent distress. Purpose To examine the trajectories of mental distress between March 10 and August 4, 2020, a key period during the COVID-19 pandemic. Methods Participants included 6,901 adults from the nationally representative Understanding America Study, surveyed at baseline between March 10 and 31, 2020, with nine follow-up assessments between April 1 and August 4, 2020. Mixed-effects logistic regression was used to examine the association between date and self-reported mental distress (measured with the four-item Patient Health Questionnaire) among U.S. adults overall and among sociodemographic subgroups defined by sex, age, race/ethnicity, household structure, federal poverty line, and census region. Results Compared to March 11, the odds of mental distress among U.S. adults overall were 1.84 (95% confidence interval [CI] = 1.65–2.07) times higher on April 1 and 1.92 (95% CI = 1.62–2.28) times higher on May 1; by August 1, the odds of mental distress had returned to levels comparable to March 11 (odds ratio [OR] = 0.80, 95% CI = 0.66–0.96). Females experienced a sharper increase in mental distress between March and May compared to males (females: OR = 2.29, 95% CI = 1.85–2.82; males: OR = 1.53, 95% CI = 1.15–2.02). Conclusions These findings highlight the trajectory of mental health symptoms during an unprecedented pandemic, including the identification of populations at risk for sustained mental distress.