Introduction: Insulin sensitivity can be measured by procedures such as the hyperinsulinemic-euglycemic clamp or using surrogate indices. Chronic kidney disease (CKD) and obesity may differentially affect these measurements because of changes in insulin kinetics and organ-specific effects on insulin sensitivity. Methods: In a cross-sectional study of 59 subjects with non-diabetic CKD (estimated glomerular filtration rate (GFR) <60 mL/min/1.73 m²) and 39 matched healthy controls, we quantified insulin sensitivity by clamp (SI_clamp), oral glucose tolerance test, and fasting glucose and insulin. We compared surrogate insulin sensitivity indices to SIclamp using descriptive statistics, graphical analyses, correlation coefficients, and linear regression. Results: Mean age was 62.6 years, 48% of participants were female, and 77% were Caucasian. Insulin sensitivity indices were 8% to 38% lower in participants with versus without CKD and 13% to 59% lower in obese compared to non-obese participants. Correlations of surrogate indices with SI_clamp did not significantly differ by CKD or obesity status. Adjusting for SI_clamp in addition to demographic factors, Matsuda index was 15% lower in participants with versus without CKD (p=0.09) and 36% lower in participants with versus without obesity (p=0.0001), while 1/HOMA-IR was 23% lower in participants with versus without CKD (p=0.02) and 46% lower in participants with versus without obesity (p<0.0001). Conclusions: CKD and obesity do not significantly alter correlations of surrogate insulin sensitivity indices with SI_clamp, but do bias surrogate measurements of insulin sensitivity toward lower values. This bias may be due to differences in insulin kinetics or organ-specific responses to insulin.