Vasoclusion crisis is a major cause of morbidity and mortality in patients with Sickle Cell Anemia (SCA). There are currently a paucity of data on the hemogram response to vasoclusive crisis in patients with SCA in the Enugu metropolis. The present study is designed to determine the hemogram response to vasoclusive crisis in SCA patients compared to steady state and controls. A total of 150 subjects comprising 75 confirmed SCA patients (35 males and 40 females) aged between 16 and 30 years from Sickle Cell Clinic and 75 apparently healthy age and gender-matched controls of the Enugu State University of Science and Technology Teaching Hospital Enugu State participated in the study. Sample size was calculated using single proportion method. Ethical clearance was obtained from the Ethical Review Board of the hospital. Informed consent was obtained from subjects. Blood sample (5.0 ml) was collected from each subject and 3.0 ml was dispensed into ethylene diamine tetracetic acid tubes for estimation of the hemogram using Mindray 530-BC hemoanalyser. The hemogram revealed significant decrease (p < 0.05) in Hemoglobin (Hb) during crisis (9.17 ± 0.91 g/dl) and during stead-state (11.63 ± 0.45 g/dl) and in hematocrit (Hct) during crisis (34.80 ± 3.03%) and during steady state (34.90 ± 1.37%) compared to controls Hb (13.5 ± 0.5 g/dl) and Hct (39 ± 1.5%). The total white blood cell count (TWBC) (8.3 ± 2.0 x 109/l) significantly increased (p < 0.05) in crisis compared to TWBC (5.2 ± 1.0 x 109/l) and (5.5 ± 0.5 x 109/l) for the steady-state and controls respectively while the Platelet (PLT) significantly increased (p < 0.05) in crisis (200 ± 55.05 x 109/l) compared to PLT (164 ± 45.39 x 109/l) and (150 ± 20.0 x 109/l) for the steady-state and controls respectively. This finding provides scientific data for changes in the hemogram in sickle cell patients during crisis and steady state.