Iron is a vital mineral for the proper function of hemoglobin which is also a protein needed to transport oxygen in the blood. The lack of iron in human blood causes a range of serious health problems including “anemia.” In this article, the COntAneRS (Clinical ONTology-based Iron Deficiency‐ANEmia‐ Recommendation System) is proposed as a clinical decision support system to diagnose iron deficiency and manage its treatment. The applied methodologies and main technical contributions of this study are discussed in four aspects: (1) Iron Deficiency Domain Ontology (IDDOnt), (2) Semantic Web Rule Knowledgebase (SWRL), (3) Inference Engine, and (4) Physician Portal of the system. Experimental studies of the proposed system have been applied on a population of 200 people, consisting of real anemia patients and healthy individuals. First, a decision tree classifier is used to diagnose iron deficiency condition based on the patients’ demographic information and certain medical data, as well as recently measured hemoglobin CBC levels of the patients. To check the effectiveness of the system, the data of 50 anonymous patients randomly selected from 200 patients are entered manually in the IDDOnt and the system is then verified according to the inferencing results. After inferencing step, the recommendations related to appropriate iron drugs, daily consumption dose, drug consumption periods, and additional medical suggestions about drug interactions are provided by the system to the responsible physician through system ontology, SWRL rules, and web services. As a result of experimental studies, our system has provided very good accuracy (99.5%) and robust results in producing patient-suitable suggestions. In addition, the applicability of the system on the cases is discussed as case studies in this paper. The results reported from the applied case studies are promising in demonstrating the applicability, effectiveness, and efficiency of the proposed approach.