Introduction: Polycystic ovary syndrome is a multifactorial disease caused by both genetic and environmental factors acting concurrently with rising prevalence at an alarming rate. It is a health problem that affects 1 out of 10 women of childbearing age. PCOS have negative impact on quality of life resulting in depression. Objective: The present study was designed to assess health related quality of life and depression among polycystic ovary syndrome patients in Pakistan. Methodology: A descriptive cross sectional study design was used to assess health related quality of life and depression among 152 women with PCOS diagnosed by Rotterdam criteria using PCOSQ-50 and HADS. Data was collected and statistically analysed. Results: Significant difference (p ≥ 0.05) among different domain of HRQoL and level of depression among women with PCOS was observed. Unmarried patients had better emotions while body hairs, weight and infertility effect married women. Rural patients had relatively poor HRQoL. Women with PCOS in age group 26-35yrs had impaired HRQoL due to infertility, emotions and increased weight. Obese patients with PCOS had relatively more impaired HRQoL as all domains were affected in them. Women with PCOS residing in rural areas were found relatively more depressed and those belonging to low educational and income background were comparatively found more depressed. Conclusion: The results of the present study concluded that polycystic ovary syndrome had a negative impact on health related quality of life of patients across all domains with a significant likelihood of depression. While all domains were affected, the greatest impact was seen on infertility followed by body hairs and role limitation due to increased psychological and emotional problems. Low educational and income background had negative effect on mental and emotional HRQoL of polycystic ovary syndrome patients and depression. More attention should be given on improvement of health related quality of life among PCOS patients to decrease the rate of treatment failure and improve treatment response.