Background: Sickle cell disease (SCD) is a lifelong condition, it has been recognized as a procoagulant state in which micro thrombi have influenced the evolution of many complications. Relating homocysteine levels to basic haemostatic indices will provide insight on contribution of thrombotic phenomena to ill health and wellness. Objective: To explore the relationship between serum homocysteine and some hematological parameters among SCA patients attending a tertiary hospital. Methods: This is a hospital-based comparative cross-sectional study that involves 60 participants comprising 30 patients with SCA and 30 HbAA controls. Hematological parameters were analyzed using an automated hematology analyzer, while serum homocysteine was determined using enzyme linked immunosorbent assay (ELISA) method. Data were analyzed using SPSS version 23. A p-value <0.05 was considered statistically significant. Results: The mean value for homocysteine in the HbSS group was 9.72 ±0.96 µmol/L whilst that of the HbAA was 6.19 ±0.88 µmol/L. There was significantly higher mean white blood cell (WBC) and platelets count in the subjects with p value of < 0.005 but significantly lower mean haemoglobin and haematocrit (P< 0.005). The mean PT and APTT of controls, 13.00 and 34.50 were more prolonged than that of subjects 12.00 and 32.00 (p = 0.001 and p < 0.0001 respectively). Conclusion: The study did not find any relationship between serum homocysteine and the hematological parameters analyzed.