Background: Mental health impacts of the COVID-19 pandemic are well recognized, but little is known about the pandemic experience among people experiencing mental health symptoms. Methods: In June 2020, a national sample of 5023 U.S. adults, including 785 scoring ⩾10 on the PHQ-8 for symptoms of depression, completed survey measures related to their pandemic experience. Results: After adjusting for sociodemographic characteristics, aspects of the COVID-19 pandemic experience for which participants scoring PHQ-8 ⩾ 10 had the greatest increase in odds of reporting moderate/severe negative impacts included: mental health treatment access (odds ratio [OR], 95% confidence interval [CI] = 8.81, 6.70-11.57), family stress/discord (OR, 95% CI = 5.21, 4.24-6.42), food access (OR, 95% CI = 3.76, 2.97-4.77), and income/employment (OR, 95% CI = 3.19, 2.66-3.83). They were also significantly more likely to report increased use of prescription painkillers (OR, 95% CI = 8.46, 4.50-15.92) and other drugs (OR, 95% CI = 4.43, 2.85-6.89), and less trust in healthcare authorities/providers, family/friends, and employers, and more trust in websites/blogs/social media, for COVID-19 information ( P-values < .05). Conclusions: The interplay among depressive symptoms, substance use, lack of trust in healthcare authorities, and negative impact of the pandemic on family, finances, and access to mental health treatment and food indicate the need for robust social and behavioral health safety nets to buffer communities from the shadow epidemics of depression, family violence, and overdose deaths during public health disasters.