INTRODUCTION: While sickle cell disease (SCD) is primarily acknowledged as an erythrocyte disorder, emerging evidence suggests a role for altered neutrophil phenotype and function in SCD pathophysiology and disease severity. Given the conflicting findings in previous studies, we performed a comprehensive exploration of neutrophil characteristics in SCD patients during steady state and vaso-occlusive crisis (VOC), as well as in response to therapeutic interventions. METHODS: Neutrophil phenotype was assessed by flow cytometry and functional properties were evaluated by measurement of neutrophil adhesion and reactive oxygen species (ROS) production. RESULTS: A total of 49 SCD patients (of whom 19 during both steady state and VOC) along with 16 healthy ethnicity-matched and 30 non-matched controls, were included in the study. Differences were observed between neutrophils from patients compared to controls and between control groups. Neutrophil phenotype was more activated in SCD patients compared to non-matched controls. Neutrophil adhesion was increased in steady-state SCD patients compared to both ethnicity-matched and non-matched controls. DISCUSSION: While neutrophil phenotype in SCD patients differed from non-matched controls, in contrast to earlier studies, the differences in neutrophil phenotype between SCD patients and ethnicity-matched controls were modest.