ObjectiveThe Low Middle Income Countries (LMIC) like Pakistan are facing an escalation in the number of HIV cases, approximately more than 180,000 people are currently living with HIV/AIDS (PLWHA). Currently, no HIV specific Health Related Quality of Life (HRQoL) tool is validated in Pakistan; therefore, the current analysis was aimed at translating and examining the psychometric properties of the Urdu version of WHOQOL HIV BREF among HIV patients of Pakistan.MethodsThe standard forward-backwards translation technique was used for Urdu translation of the instrument. Based on the principle of 5 subjects minimally for each item, a sample of 182 patients were recruited by employing a universal random sampling technique. Data were analysed to measure reliability, internal consistency, known-group, multivariable linear regression and construct validity. Results High internal consistency 0.93 (Cronbach alpha) was found for all WHOQOL HIV Bref facets. The test-retest reliability analysis demonstrated a statistically significant Interclass Correlation Coefficient (ICC) ranged from 0.88 – 0.98 (p < 0.001). In known group validity, lower CD-4 lymphocytes count was significantly related to poor scores for all six domains (p < 0.001). Similarly, symptomatic subjects had significantly lower scores compared to asymptomatic subjects on the physical, psychological, social relationship and independence domains (p < 0.05). Results also revealed a statistically significant positive correlation of all six domains with CD4 count (p < 0.001), exhibiting patients with higher CD-4 lymphocytes count will have higher mean scores of all six domains. Factor analysis revealed 5 domains, including Physical health, Psychological health, Social relationship, Environmental, and Spiritual health. When all domains were assessed together via Multivariable linear regression analysis; only physical, psychological health and environment health domains were found significantly associated with higher CD-4 lymphocytes count (Beta = 0.121, p < 0.001, Beta = 0.103, p = 0.002, and Beta = 0.032, p = 0.032).ConclusionFindings suggested that the Urdu version of WHOQOL HIV Bref is a psychometrically valid tool for measuring HRQoL.