Allium sativa (garlic) is a bulbous herb used as food item, spice and medicine in different parts of the world. The effect of garlic (Allium Sativa) on the osmotic fragility of red blood cells in normal and sickle cell patients was assessed in vitro. The study comprised four sets of fourteen centrifuge tubes each containing 5ml of graduated concentrations of normal saline. To the first set of tubes, 20µl of blood from normal subjects was added using a micropipette, while to the second, 0.75mg of garlic and 20µl of blood from normal subjects were added. To the third set of tubes, 20µl of blood from sickle cell patient was added, and to the fourth 20µl of blood from sickle cell patient and 0.75mg of garlic were added. Percentage hemolysis was determined by spectrophotometry. It was observed that the degree of hemolysis was greater (P<0.05) in the sickle cell compared to the normal blood. This observation was also recorded in the samples treated with garlic. It is concluded that the degree of hemolysis in sickle cell is higher (P<0.05) than normal cell. Treatment with garlic increased fragility in both normal and sickle cell blood however this effect was more pronounced in sickle cell blood. It is recommended that the consumption of garlic in patients with sickle cell anemia should be continuously monitored and carefully regulated.