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OBJECTIVES: Human immunodeficiency virus (HIV) rates in the southeast United States are high and substance use is common among people living with HIV (PLWH). This study used baseline data from the weCare intervention study to examine factors associated with the use of alcohol, tobacco, and marijuana among racially and ethnically diverse young gay, bisexual, and other men who have sex with men (GBMSM) and transgender women in the southeast who were newly diagnosed as having HIV, not linked to care, out of care, and/or not virally suppressed. METHODS: Self-reported data were collected from 196 GBMSM and transgender women living with HIV via Audio Computer-Assisted Self-Interview at enrollment. Measures assessed demographics; stigma; social support; basic and clinical service needs; HIV disclosure; social media use; and recent use of alcohol, tobacco, and marijuana. Logistic regression identified correlates of past 30-day substance use. RESULTS: In multivariable analysis, increased age and needing basic support services were associated with past 30-day tobacco, cigarette, electronic cigarette, and/or hookah use. Increased HIV-related stigma and needing basic support services were associated with past 30-day marijuana use. Being White and needing clinical support services were associated with infrequent or no past 30-day marijuana use. CONCLUSIONS: HIV-related stigma and needing basic support services were associated with substance use among GBMSM and transgender women living with HIV in the southeastern United States. Routine screening for basic needs could identify GBMSM and transgender women living with HIV at risk for substance use and offer insight into intervention leverage points.