Background and Objective: While a large proportion of fever among children in sub-Saharan Africa is accompanied by malaria, malaria is not always the main cause of fever. In areas of high malaria prevalence, antimalarials are frequently over-prescribed. Our objective was to achieve a better understanding of malaria infection dynamics and hospital diagnoses in an area where malaria is highly endemic. Methods: The fever without source study was conducted 2013-2015 at Agogo Presbyterian Hospital (APH) in Agogo, Ghana. Febrile children under 15 admitted to the pediatric ward were recruited to the study. Demographic, clinical, and laboratory data were collected and analyzed descriptively and graphically in r. Results: A total of 1503 admissions were included in the analysis. Malaria parasites were detected in a majority (59%) of patients but analysis of changes in practitioner diagnoses from admission to discharge revealed that sepsis and malaria were frequently over-diagnosed: almost one-third of malaria and over 80% of sepsis admission diagnoses were not confirmed at discharge. Among children with malaria parasites detected in the blood, 95% received antimalarial treatment and 52% received antibiotics. Among those without malaria parasites, 30% were given antimalarials and 95% were given antibiotics. Conclusions: Adherence to World Health Organization guidelines for the management of malaria and clearer diagnostic guidelines for the diagnosis of non-malarial febrile illness are needed. Further development of these guidelines could improve hospital diagnoses, reduce delays in treatment, and minimize unjustified antibiotic prescription.