Anemia is a common and serious complication of malaria due to infection, a major health problem in tropical areas. Herein, the relation was investigated between the levels of circulating erythropoietin (EPO) and immunomodulatory cytokines in response to chloroquine treatment. Thirty-seven healthy control subjects and 40 patients with acute infection were included in the study. All subjects were adult male Sudanese. Blood samples were collected before chloroquine administration (25 mg/kg body weight, orally on three consecutive days) and 3 and 30 days after start of the therapy. Measurements included routine hematological parameters and the concentrations of immunoreactive EPO, tumor necrosis factor-α (TNF-α), interleukin 1α (IL-1), IL-6, and interferon γ (INF-γ). Chloroquine treatment led to a decrease in EPO levels in the control subjects but an increase in malaria patients at day 30. The latter was likely due to the anti-inflammatory action of the drug because INF-γ, IL-1, and IL-6 concentrations declined on chloroquine treatment. Based on these findings, we propose that an impaired EPO production in association with a prolonged elevation of certain inflammatory cytokines can contribute to the anemia in some malaria patients which can be reversed by chloroquine therapy.