Background: The risk of chronic inflammatory conditions along with disturbed iron metabolism is markedly increased in postmenopausal women. This study investigated iron biomarkers and their association with hepcidin and sCD163 among postmenopausal women. Methods: The study included ninety Jordanian women divided into two groups: premenopausal group (PRE, n = 41), and postmenopausal (POST, n = 49). Anthropometric measures, ferritin, iron, hemoglobin, transferrin, TIBC, hepcidin, sCD163, and hs-CRP were assessed in Serum levels of ferritin, iron, transferrin, TIBC, hs CRP and estrogen were determined by chemistry autoanalyzer. Hepcidin and sCD163 levels were determined by ELISA. Results: The study showed that hemoglobin and ferritin were significantly higher in postmenopausal subjects than premenopausal subjects (p values < 0.005). The mean levels of hepcidin and sCD163 were significantly lower in POST than in PRE subjects (67.7 + 16.0 versus 78.6 + 33.2 and 12.3 + 3.7 versus 18.5 + 15.4, p = 0.034 and 0.019; respectively). Significantly higher levels of hs-CRP were observed in postmenopausal subjects as compared to premenopausal subjects (p = 0.006). Among postmenopausal women, significant positive correlations were observed between hepcidin and each of ferritin, sCD163 and hs-CRP (r = 0.451, p = 0.031, r = 0.379, p = 0.007 and r = 0.366, p = 0.010) respectively). Conclusion: The altered iron metabolism among postmenopausal women is related to an interaction between hepcidin, sCD163, and hs-CRP. This interaction might be attributed to the inflammatory condition during the postmenopausal stage of women’s life.