As people living with HIV experience longer life-expectancies resulting from antiretroviral therapy, comorbid conditions are increasing, particularly metabolic disorders. There is potential for psychosocial factors such as stigma experiences, depression, and alcohol use to complicate both HIV infection and metabolic disorders, including diabetes mellitus and hyperlipidemia. While the impact of these psychosocial factors on HIV infection alone are widely studied, their role in potentially complicating HIV co-morbid metabolic conditions has received little attention. This study examined the association between HIV-related stigma and depression, and the potential role of alcohol use as a mediating factor in a clinical sample of patients with comorbid HIV infection and metabolic conditions. Results demonstrated that HIV stigma is associated with depression and this relationship is in part accounted for by alcohol use. Our results indicate that interventions aiming to improve the health of people living with HIV and co-morbid metabolic disorders should prioritize addressing alcohol use as it is related to sources of stress, such as stigma, and depression.