RATIONALE & OBJECTIVE: Health-related quality of life (HRQoL) is a major outcome measure increasingly used in patients with chronic kidney disease (CKD). We evaluated the association between different stages of CKD and the physical and mental health domains of HRQoL. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 2,693 outpatients with moderate (stage 3, estimated glomerular filtration rate [eGFR], 30-60mL/min/1.73m2) or advanced (stages 4-5, estimated glomerular filtration rate<30mL/min/1.73m2, not on kidney replacement therapy [KRT]) CKD under the care of a nephrologist at 1 of 40 nationally representative facilities, 1,658 patients with a functioning kidney transplant, 1,251 patients on maintenance dialysis randomly selected from the national Renal Epidemiology and Information Network registry, and 20,574 participants in the French Decennial Health Survey, representative of the general population. PREDICTOR: Severity of kidney disease (moderate CKD, advanced CKD, maintenance dialysis as KRT, and functioning kidney transplant as KRT), compared with a sample of the general population. OUTCOMES: HRQoL scores assessed using the Medical Outcomes Study 36-Item Short Form Health Survey or the Kidney Disease Quality of Life 36 scale. ANALYTICAL APPROACH: Age- and sex-standardized (to the general population) prevalence of poor or fair health status was estimated for each study kidney disease group. Analysis of variance was used to estimate adjusted differences in mean physical and mental health scores between the kidney disease subgroups and the general population. RESULTS: Mean age was 67.2±12.6 (SD) years for patients with non-KRT-requiring CKD, 69.3±17.7 years for dialysis patients, and 55.3±14.2 years for those with functioning kidney transplants; 60% were men. Age- and sex-standardized health status was perceived as fair or poor in 27% of those with moderate CKD,>40% of those with advanced CKD or receiving dialysis, 12% with a functioning transplant, and 3% of the general population sample. HRQoL physical scores (adjusted for age, sex, education, obesity, and diabetes) were significantly lower in patients in all CKD subgroups than in the general population. For patients receiving dialysis, the magnitude of the difference in physical score versus the general population exceeded 4.5 points, the minimal clinically important difference for this score in this study; for both kidney transplant recipients and patients with advanced CKD, the magnitude of the difference was close to this threshold. For mental score, only dialysis patients had a score that differed from that of the general population by more than the minimal clinically important difference. LIMITATIONS: Cross-sectional study design for each subpopulation. CONCLUSIONS: This study highlights the degree to which perceived physical health is lower in the setting of CKD than in the general population, even in the absence of kidney failure, and calls for greater attention to CKD-related quality of life.