BACKGROUND: Low high-density lipoprotein (HDL) cholesterol level is common in patients with chronic kidney disease, but associations between severity of chronic kidney disease, obesity, and HDL level have not been well defined. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Within a large integrated health care delivery system, we identified all adult individuals without diabetes who had measured kidney function (estimated glomerular filtration rate [eGFR]), body mass index (BMI), and HDL level, but no substantial proteinuria, confounding medications, or prior renal replacement therapy. PREDICTORS: The primary predictors for our analyses were eGFR and BMI. OUTCOMES: Low HDL cholesterol level was the outcome. We performed multivariable logistic regression to investigate whether the relationship between BMI and low HDL level (men, <40 mg/dL; women, <50 mg/dL) varied as a function of eGFR. RESULTS: Of 380,207 individuals who met cohort entry criteria, there were 26,089 (7%) with chronic kidney disease by eGFR level. Compared with eGFR of 60 mL/min/1.73 m(2) or greater, lower eGFR category (in mL/min/1.73 m(2)) was associated with an increased adjusted odds of low HDL level independent of BMI and other confounders. However, there was a significant interaction between eGFR and BMI (P < 0.001). In separate models stratified by eGFR category (>or=60, 45 to 59, and 30 to 44 mL/min/1.73 m(2)), greater BMI was associated with a graded increased adjusted odds of low HDL level in each eGFR category, but this relationship was attenuated in patients with lower eGFR. LIMITATIONS: Information for undiagnosed diabetes and proteinuria was unavailable. CONCLUSIONS: Decreased eGFR is independently associated with greater odds of having a low HDL level. Across a spectrum of eGFR, greater BMI was associated with lower HDL level, but the magnitude of this association was diminished at lower eGFR, suggesting that other factors may also contribute to low HDL levels in patients with advanced chronic kidney disease.