BACKGROUND AND OBJECTIVES: Persons with ESRD identify non-disease-specific conditions as negatively affecting their quality of life. It is unknown how these non-ESRD-specific conditions correlate with each other and with ESRD-specific conditions such as anemia, renal osteodystrophy, dialysis access, and dialysis adequacy. The objectives of this study were to determine the prevalence and inter-relatedness of selected conditions among persons receiving hemodialysis and to analyze the relationship between non-ESRD-specific and ESRD-specific conditions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was an observational cohort study of persons with ESRD that included standardized assessments for pain, fatigue, depression, cognitive impairment, and impaired physical performance. The study was conducted at three dialysis clinics in one urban geographic area. Of the 134 persons who met exclusion criteria, 25 declined participation, yielding a sample size of 109. RESULTS: Pain was present in >81% of participants, fatigue and impaired physical performance in >60% participants, and cognitive impairment and depression in >25% of participants. Pain, fatigue, and depression were highly correlated, but had no correlation with use of a catheter for access, hemoglobin (Hgb), intact parathyroid hormone (iPTH), phosphorous, or Kt/V values outside of the range of guidelines. There was a modest correlation between cognitive function and both Hgb and iPTH. CONCLUSIONS: Non-ESRD-specific conditions such as fatigue, pain, and depression are as prevalent as ESRD-specific conditions, and the magnitude of the correlations between the non-ESRD-specific conditions is greater than the correlations between non-ESRD-specific and ESRD-specific conditions. Current guidelines may be failing to address a substantial component of the disease burden for persons with ESRD.