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Background: Sickle cell disease (SCD) is a diverse group of blood disorders with significant global disease burden. Contemporary interest in the underlying inflammatory paradigm of SCD has emphasized the role of the neutrophil-lymphocyte ratio (NLR) as a prognostic inflammatory marker., Methods: We retrospectively reviewed 268 hospitalized patients with SCDs of different genotypes (HbSS, HbSβ 0 thalassemia, HbSβ + thalassemia, and HbSC), totaling 3329 hospital admissions over a 10-year period. Patients were stratified into SS/Sβ 0 and Sβ + /SC groups for statistical analysis of parameters collected at steady state and at hospital admission., Results: At steady state, per unit increase of hemoglobin values was associated with reduced odds of ≥ 2 hospital admissions per year in SS/Sβ 0 and Sβ + /SC groups; per unit increase in platelet count and white blood cell count was associated with increased odds only in the SS/Sβ 0 group. The NLR had no association in either group. During admission, a cutoff of NLR = 3.5 discerned infection with a sensitivity of 60% and specificity of 57%. Performance improved when excluding patients on outpatient hydroxyurea therapy (cutoff of NLR = 3.5; sensitivity of 68% and specificity of 64%)., Conclusion: This study supports the utility of NLR as an accessible adjunctive clinical tool in SCD prognostication.