This study examined the pattern of psychoactive substance use among young people living with HIV/AIDS (YPLWHIV/AIDS) attending a tertiary health institution in Ekiti State, Nigeria. A descriptive cross-sectional design using a quantitative approach was adopted, involving 204 sero-positive clients aged 10–35 years receiving care at the Antiretroviral Therapy and Counselling (ART&C) unit of Ekiti State University Teaching Hospital, Ado-Ekiti. Participants were selected through simple random sampling, and data were collected using an adapted version of the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test (WHO-ASSIST). Findings revealed that psychoactive substance use was common among respondents, with alcohol being the most frequently used substance, followed by tobacco, non-prescribed medications, and locally available mixtures. Patterns of use were characterized by predominant oral intake, self-medication without prescription, and frequent combination of substances, raising concerns about potential drug interactions and adverse health outcomes. Although substance use cut across all age groups and genders, marital status and educational qualification significantly influenced patterns of use, highlighting the protective role of social support and health literacy. Age, gender, occupation, and residence showed limited influence on substance use patterns. The study underscores the need for integrating substance-use screening, counselling, and targeted health education into HIV care services to improve treatment adherence and overall well-being among YPLWHIV/AIDS. Keywords: Psychoactive substance use; Young people; HIV/AIDS; Drug use pattern; WHO-ASSIST,