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Background: Although hematological indices cannot in entirety be used to diagnose diseases or defects, the appropriate interpretation of these indices could complement diagnostics such as microscopy and serology for numerous illnesses in children. This study sought to evaluate distinct hematological indices characterizing different childhood illnesses., Methods: Full blood counts from 150 children (age range from 1 to 15 year) presenting different disease conditions at the Tamale Central Hospital were assessed. The hematological indices were compared between disease categories, and relationships between disease indicators were determined., Results: The prevalence of the diagnosed childhood illness were: 50.7% malaria, 20.0% diarrhea, 13.3% typhoid fever, 10.0% Sickle Cell Disease (SCD), and 6.0% malaria-typhoid co-infection. Fever was diagnosed in a majority (66.0%) of the children, but was independent of each disease group, (χ 2  = 9.18, P = .057). Of the 24 hematological indices analyzed, eight; red blood cell (RBC) (P < .001), hemoglobin (Hb) (P < .001), mean cell volume (MCV) (P = .002), mean cell hemoglobin (MCH) (P < .001; lowest and below normal range for SCD), red cell distribution width (RDW&#95;CV) (P < .001), eosinophil percentage [EOS (%)] (P = .001), eosinophil number [EOS#] (P = .002), and platelets (PLT) (P = .001; lowest for malaria) differed significantly across the different disease groups. Levels of Hb and/or MCV were below the normal reference ranges for most of the diagnosed diseases. In addition, low PLT and MCH were respectively distinct for children with malaria and SCD., Conclusion: Hematological indices including Hb, MCV and PLT, or MCH may be useful indices that could incite further diagnostic tests for malaria or SCD among children in Ghana., (© 2018 Wiley Periodicals, Inc.)