Abstract Background: The incidence rate of anemia of chronic disease (ACD) in systemic lupus erythematosus (SLE) ranges between 30 and 80%. Serum iron is the main regulator of hepatic hepcidin production. Interleukin-6 (IL-6) upregulates hepcidin expression. The aim of this study is to compare between serum hepcidin and IL-6 in SLE patients and control subjects, and to find out if they are correlated with each other and with disease activity in order to find their role in treatment of anemia in SLE patients. The study was carried out on 50 SLE patients, suffering from anemia, diagnosed according to SLICC revision of the ACR classification criteria for SLE, and 50 healthy individuals, taken as control. Disease activity was assessed using the SLE disease activity index (SLEDAI-2 K). Serum hepcidin and IL-6 were measured by ELISA kit. Results: There was a highly statistically significant difference in serum hepcidin and IL-6 levels between patients and control subjects. There was a statistically significant correlation between serum hepcidin and IL-6 in SLE patients. Moreover, both of them were correlated with SLEDAI and ESR and negatively correlated with hemoglobin. The mean value of serum hepcidin in SLE patients with normocytic normochromic anemia was higher than that in patients with microcytic hypochromic anemia. However, this difference did not reach a statistically significant level. Conclusion: High serum IL-6 and hepcidin levels are associated with anemia in SLE. They are correlated with each other and with disease activity. Although our study revealed serum hepcidin to be correlated with disease activity, it should not be used as a marker of disease activity in SLE patients as our patient’s group was SLE patients suffering from ACD. However, IL-6 inhibition should be considered in patients with SLE with anemia to guide the control of anemia of chronic diseases resulting from cytokine production as a result of high disease activity in SLE patients. It should be noted that the occurrence of ACD associated with IL-6 flare up could be a player in other systemic rheumatic diseases and is not specific to SLE patients.