Background HIV, substance use and trauma are associated with more severe symptoms and poorer outcomes in psychosis. We aim to describe the profile of adults with first episode psychosis (FEP) and associations with substance use and trauma in a cohort of patients in a low resource, high HIV prevalence setting in South Africa. Methods We recruited all adult patients (18–45 years) presenting with FEP to five psychiatric units in the eThekwini Municipality, KwaZulu-Natal Province. Psychiatric diagnosis was made using the MINI. We used the PANSS for psychotic symptoms, WHO ASSIST for substance use and CTQ for early childhood trauma. HIV status was confirmed by ELISA. Results Sixty participants were recruited, mean age 26 years (SD 8, IQR 19–33), 68% (n=41) were male. Mean age at presentation was 24 and 31 years for males and females respectively, with males being significantly younger than females (p=0.0003). Duration of untreated psychosis (DUP) was 12.5 months (IQR 1–10.3 months). Lifetime tobacco, alcohol and cannabis use was reported at 57%, 55%, and 47% respectively. Substance use was more prevalent among males compared to females, p=0.10, 0.13 and 0.0001 for tobacco, alcohol and cannabis respectively. Lifetime cannabis use was associated with higher negative PANSS scores (mean score 32, SD 10) compared to non-users (mean score 17, SD 7), p=0.05. Sixty eight percent (n=41) reported any traumatic event. Sixty-two percent (n=37) experienced trauma before 18 years and 35% (n=21) reported traumatic experiences in adulthood. Individuals who reported trauma in adulthood had higher hostility scores in the PANSS compared to those who experienced no trauma in adulthood (p=0.05). Fifteen (25%) of the cohort was HIV infected. Females were more likely to be HIV infected (58% HIV infected females compared to 9.8% HIV infection in males, p=0.0001). Eleven of the 15 HIV infected patients had been on antiretroviral treatment prior to the psychosis onset and four were newly diagnosed at the time of psychosis presentation. Of the 11 individuals on antiretroviral treatment, 6 (45%) were virologically suppressed. There was no significant difference in PANSS scores by HIV status (p=0.5) and childhood trauma (p=0.5). Discussion The study found participants with FEP had a high prevalence of HIV, particularly in females, and high prevalence of tobacco, alcohol and cannabis use. This suggests that these individuals are particularly vulnerable to the triple burden of psychosis, substance use and HIV. In addition, they had long DUP suggesting delay in accessing treatment, which all serve as poorer prognostic indicators in an already overwhelmed health care setting. The high rates of trauma (more than half the sample reporting childhood trauma) is another major public health concern as trauma exposure has been associated with poorer physical and mental health outcomes. In this study the lack of association between childhood trauma and psychosis severity is inconsistent with literature and needs to be further explored. The association between adult exposure to trauma and increased hostility scores suggests the need to include psychological treatment strategies to address the trauma exposure to improve outcomes.