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The objective was to examine the impact of the COVID-19 pandemic on mental health care, cannabis use, and behaviors that increase the risk of STIs among men living with or at high risk for HIV. Data were from mSTUDY — a cohort of men who have sex with men in Los Angeles, California. Participants who were 18 to 45 years and a half were HIV-positive. mSTUDY started in 2014, and at baseline and semiannual visits, information was collected on substance use, mental health, and sexual behaviors. We analyzed data from 737 study visits from March 2020 through August 2021. Compared to visits prior to the COVID-19 pandemic, there were significant increases in depressive symptomatology (CES-D ≥ 16) and anxiety (GAD-7 ≥ 10). These increases were highest immediately following the start of the pandemic and reverted to pre-pandemic levels within 17 months. Interruptions in mental health care were associated with higher substance use (especially cannabis) for managing anxiety/depression related to the pandemic (50% vs. 31%; p-value <.01). Cannabis use for managing pandemic-related anxiety/depression was higher among those reporting changes in sexual activity (53% vs. 36%; p-value = 0.01) and was independently associated with having more than one sex partner in the prior 2 weeks (adjusted OR = 1.5; 95% CI 1.0–2.4). Our findings indicate increases in substance use, in particular cannabis, linked directly to experiences resulting from the COVID-19 pandemic and the associated interruptions in mental health care. Strategies that deliver services without direct client contact are essential for populations at high risk for negative sexual and mental health outcomes. [ABSTRACT FROM AUTHOR]