Background: Patients' health-related quality of life (HRQoL) is an important indicator for predicting the effectiveness of treatment, morbidity, and mortality. The aim of this study was to determine the level of HRQoL and the most important factors affecting HRQoL in patients receiving peritoneal dialysis (PD). Methods: This cross-sectional study was performed with 156 patients, 30 of whom (19.2%) had automated PD (APD), were over 18 years of age, and were followed up at the Erciyes University Continuous Ambulatory Peritoneal Dialysis (CAPD) Unit during the previous year. HRQoL, depression, and fatigue were measured by means of the Short Form-36 (SF-36), Beck Depression Inventory (BDI), and Fatigue Severity Scale (FSS), respectively. Results: The mean mental component summary (MCS) score was 42.1 +/- 11.9 and physical component summary (PCS) score was 39.1 +/- 11.2, which was lower than MCS. Depression was the strongest predictor for both diminished mental (beta = -24.4, p < 0.001) and physical (beta = -16.5, p < 0.001) HRQoL. Fatigue was the next strongest predictor for diminished physical HRQoL only (beta = -7.74, p < 0.001). Depression and fatigue accounted for 37% of physical HRQoL impairment. Depression as a sole factor was responsible for 31% of mental HRQoL impairment. Age, hospitalization, total cholesterol, serum albumin levels, and Kt/V urea had affected the SF-36 in some domains score but not in all. Conclusion: HRQoL in our PD patients can be evaluated at a slightly poor level compared to the results of previous studies. Impaired HRQoL is more closely associated with depression and fatigue. Depression was the strongest predictor of both mental and physical HRQoL. Fatigue was the next strongest predictor for physical HRQoL only.