Hyper-reactive malarial splenomegaly (HMS) is a significant complication of chronic malaria, particularly in endemic regions. This study aimed to assess the prevalence and associated clinical parameters of HMS among febrile and non-febrile children under ten years of age in selected hospitals in South West, Nigeria. A cross-sectional study was conducted from September to October 2020 in Ifako General Hospital, Lagos State, and State Hospital Ota, Ogun State. A total of 130 children under ten years of age were recruited, with informed consent obtained from their parents. Venous blood samples were collected and analyzed for anti-malarial antibodies using Enzyme-linked Immunosorbent Assay (ELISA), malaria parasite detection via Rapid Diagnostic Test (RDT) and blood film examination, and complete blood count (CBC) using an auto-analyzer. A total of one hundred and thirty (130) questionnaires were administered to respondents and they were all retrieved. Out of the 130 questionnaires administered, only 88 were valid. This was due to irregular, incomplete and inappropriate responses to some questionnaires. Out of these, 9.1% were diagnosed with HMS. The study found significant associations between HMS and abnormal packed cell volume (PCV) (p = 0.023), white blood cell count (WBC) (p = 0.000), and body temperature (p = 0.009). The majority of children with HMS had abnormal WBC counts (87.5%) and low PCV levels (100%). Malaria parasites were detected in 90.9% of the participants, with the prevalence being higher among children with HMS. The study also observed no significant association between HMS and platelet count or lymphocyte levels. The study highlights a notable prevalence of HMS among children in South West Nigeria, with significant associations between HMS and certain hematological parameters. These findings underscore the need for enhanced malaria control efforts and early diagnosis to prevent HMS and related complications.