Iron (δ56Fe) and copper (δ65Cu) stable isotope compositions in blood of adult human include a sex effect, which still awaits a biological explanation. Here, we investigate the effect of menopause by measuring blood δ56Fe and δ65Cu values of aging men and women. The results show that, while the Fe and Cu isotope compositions of blood of men are steady throughout their lifetime, postmenopausal women exhibit blood δ65Cu values similar to men, and δ56Fe values intermediate between men and premenopausal women. The residence time of Cu and Fe in the body likely explains why the blood δ65Cu values, but not the δ56Fe values, of postmenopausal women resemble that of men. We suggest that the Cu and Fe isotopic fractionation between blood and liver resides in the redox reaction occurring during hepatic solicitation of Fe stores. This reaction affects the Cu speciation, which explains why blood Cu isotope composition is impacted by the cessation of menstruations. Considering that Fe and Cu sex differences are recorded in bones, we believe this work has important implications for their use as a proxy of sex or age at menopause in past populations. Am J Phys Anthropol 153:280–285, 2014. © 2013 Wiley Periodicals, Inc.