Iron deficiency (ID), the leading cause of anemia and the most common nutritional deficiency globally, is not well reported among children in malaria-endemic settings, and little is known about its contribution to anemia in these settings. We aimed to assess the prevalence of anemia, the role of ID using multiple parameters, and the factors associated with anemia in a malaria-endemic rural area. We conducted a community-based cross-sectional study of 432 children aged 1–5 years from the Popokabaka Health Zone, Democratic Republic of Congo. Sociodemographic characteristics, medical history, anthropometric parameters, and biochemical parameters were considered. Hemoglobin and malaria prevalence were assessed using rapid finger-prick capillary blood testing in the field. Venous blood samples were analyzed for serum ferritin, serum iron, total iron-binding capacity, and C-reactive protein (CRP) in a laboratory. Anemia was found in 294 out of 432 (68%) patients. Malaria was found in 375 out of 432 (87%), and ID in 1.8% according to diagnosis by adjusted ferritin only and in 12.9% according to transferrin saturation. ID indicators were not significantly correlated with low hemoglobin levels. Malaria, fever, and CRP > 5 mg/L were major factors associated with anemia in Popokabaka. Anemia control should focus on treating inflammatory conditions and infectious diseases among children in such settings.