Sickle cell anaemia (SCA) is a lifelong condition; it has been recognised as a procoagulant state in which micro thrombi have influenced the evolution of many complications. Elevated homocysteine is linked to increased risk of vaso-occlusion crisis and hyperhaemolytic crisis. This was a cross sectional study conducted in adult with sickle cell anaemia (SCA) in steady state in Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Kaduna Nigeria. Aim: To determine serum homocysteine levels in adult SCA patients in steady state and compare with those with HbAA phenotypes. Materials and Method: This cross-sectional case control study was conducted in a tertiary hospital in Zaria, Nigeria among adult HbSS patients in steady state from January to May 2023. A total of 60 participants were enrolled, 30 subjects diagnosed with SCA and 30 HbAA controls. Serum homocysteine of all participants was performed with enzyme-linked immunosorbent assay and comparison made between the subjects and controls. The Statistical Package for Social Science software (SPSS) version 23.0 was used for data analysis. 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. All the thirty (100%) SCA patients had homocysteine levels between 5-15 µmol/L whilst twenty-seven (90%) out of thirty participants in the HbAA group had homocysteine between 5-15 µmol/L. Three (10%) out of thirty in the HbAA group had homocysteine levels < 5 µmol/L. There was a statistically significant difference between the means of the two groups with p value of < 0.0001. Conclusion: This study demonstrated higher mean serum homocysteine levels among the HbSS participants in comparison with the controls (HbAA).