Background: Regional variations in size and parenchyma echo-texture of the spleen among sickle cell disease (SCD) patients have been documented in various publications. The objectives of this study were to assess the size and parenchyma echo-texture of the spleen of SCD patients and ascertain the relationship of age, height and weight with the spleen sizes. Methods: This was a cross sectional study involving 103 each of SCD and age matched control subjects. Aloka ST-550 -3500 ultrasound machine with 3.5 and 5 MHz convex transducers was used to scan the subjects over a 15 months period (September, 2012 to November, 2013. The age, height and weight of each subject were recorded. Results: The spleen sizes of SCD patients were generally larger than those of the controls (p < 0.05). Abnormal spleen parenchyma of varied appearances was found among the SCD subjects. There were negative correlations between mean spleen sizes and height, weight and age in SCD patients but positive correlations were found between them in the controls. Conclusion: Routine sonographic assessment of spleen size and echo-texture is useful in the management of SCD patients. Sci. 2015;15(3):949-58. doi: http://dx.doi.org/10.4314/ahs.v15i3.32