Background: HIV, a communicable disease, is assuming an alarming epidemic dimension with increasing level of psychiatric co-morbidity and mortality. These psychiatric comorbidities appear to be generally under-recognized and under-treated by clinicians. Aim: The aim of this study, therefore, was to determine the pattern and prevalence of psychiatric co-morbidity among PLWHIV attending the virology clinic of UPTH. Methodology: Following ethical approval from the ethical committee of the hospital and informed consent from the participants, 230 subjects were recruited based on the study’s inclusion and exclusion criteria, via a systematic random sampling. PLWHIV were further administered with the study’s instruments including the socio-demographic questionnaire and GHQ-12. The data were analyzed using the SPSS version 20 statistical package. Confidence interval was set at 95% while P- value of less than 0.05 was considered statistically significant. Results: One hundred and sixty (69.6%) out of the total number of 230 PLWHIV studied had no psychiatric diagnosis while 70 (30.4%) had different associated psychiatric morbidity. Of the total number with psychiatric diagnosis, 38 (16.0%) had depressive illness. Generalized anxiety disorder was diagnosed in 8 (3.5%) respondents, while 4 (1.7%) respondents had mixed anxiety and depression. Nine (9) (3.8%) patients had adjustment disorder while 3 (1.3%) females were diagnosed with hyposexual dysfunction. Six (2.6%) patients had alcohol abuse, 11 (5.8%) were diagnosed with PTSD and only 1 patient (0.4%) had panic disorder. Conclusion: The findings of this study support the impression that HIV infection is a chronic debilitating illness, associated with psychiatric co-morbidity. The results support the call that the management of patients with HIV should include attention to their mental health status in order to enhance the quality of care.