Abstract Introduction The current epidemic of chronic kidney disease (CKD) in Sri Lanka is ascribed to the exponential increase in the number of CKD patients, which cannot be attributed to any known etiology (CKDu). The aim of this study is to describe the health related quality of life (HRQOL) and the associated factors among CKD/CKDu patients in a rural district in Sri Lanka. Methods A community based cross-sectional study included 1174 CKD/CKDu patients. Kidney Disease Quality of Life-Short Form was used to assess the HRQOL, while Centre for Epidemiologic Studies Depression Scale, General Health Questionnaire (GHQ) 12 and CKD Symptom Index – Sri Lanka were used to assess presence of depression, psychological distress and symptom burden respectively. Three summary scores; kidney disease (KDSC), physical (PCS) and mental (MCS) are derived from Kidney Disease Quality of Life-Short Form (KDQOL-SF™). Results Mean age of the study population was 58.3 years (standard deviation (SD) 10.7). Median KDSC (58.4; inter-quartile range (IQR) 54.2–63.4), was higher than the median scores of PCS (35.0; IQR 26.2–41.9) and MCS (58.4; IQR 54.2–63.4). Multiple linear regression revealed low income, advanced stages of CKD, symptom burden, being positive for depression and psychological distress were significantly associated with low HRQOL. Conclusion The HRQOL of the CKD patients in this rural Sri Lankan population was found to be poor. Superior socio-economic status, less physical and psychological symptom burden were found to be independently associated with better HRQOL. Periodical screening of the CKD patients for depression and psychological distress and measures to alleviate symptom burden seem to be important to improve the HRQOL of these patients.