The nitrogen isotope ratio (δ15N) of RBCs has been proposed as a biomarker of marine food intake in Yup'ik people based on strong associations with RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). However, EPA and DHA derive from marine fats, whereas elevated δ15N derives from marine protein, and these dietary components may have different biologic effects. Whether δ15N is similarly associated with chronic disease risk factors compared with RBC EPA and DHA is not known. We used covariate-adjusted linear models to describe biomarker associations with chronic disease risk factors in Yup'ik people, first in a smaller (n = 363) cross-sectional study population using RBC EPA, DHA, and δ15N, and then in a larger (n = 772) cross-sectional study population using δ15N only. In the smaller sample, associations of RBC EPA, DHA, and δ15N with obesity and chronic disease risk factors were similar in direction and significance: δ15N was positively associated with total, HDL, and LDL cholesterol, apolipoprotein A-I, and insulin-like growth factor binding protein-3 (IGFBP-3), and inversely associated with triglycerides. Based on comparisons between covariate-adjusted β-coefficients, EPA was more strongly associated with circulating lipids and lipoproteins, whereas δ15N was more strongly associated with adipokines, the inflammatory marker interleukin-6, and IGFBP-3. In the larger sample there were new findings for this population: δ15N was inversely associated with blood pressure and there was a significant association (with inverse linear and positive quadratic terms) with adiponectin. In conclusion, δ15N is a valid measure for evaluating associations between EPA and DHA intake and chronic disease risk in Yup'ik people and may be used in larger studies. By measuring δ15N, we report beneficial associations of marine food intake with blood pressure and adiponectin, which may contribute to a lower incidence of some chronic diseases in Yup'ik people. J. Nutr. 144: 706-713, 2014.