Problem statement: Splenectomy is accompanied by a lifelong risk of overwhelming post splenectomy infection, mainly caused by encapsulated bacteria such as Streptococcus pneumoniae. The mortality rate in those infected patients remains high. Therefore the pneumococcal polysaccharide vaccine has been recommended. Approach: To obtain information on the immunity levels of pneumococcal antibody, in splenectomized ?-thalassemia patients in south of Iran. Patients and methods: This descriptive and cross sectional study was carried out on 263 splenectomized ?-thalassemia patients in south of Iran, June 2007-September 2008. Anti-pneumococcal vaccine antibody concentrations were measured by the enzyme-linked immunosorbent assay method. The patients were divided into two groups based on antibody concentrations: Group 1: Hyporesponsiveness patients or non-immune with less than 250 mU mL-1 antibody concentrations and group 2: Immune patients or responder with equal or more than 250 mU mL-1 antibody concentrations. Results: The results showed that 33.80 and 66.20% of the patients were immune and non-immune to pneumococcal infections, respectively. There was an inverse significant between Immunity level with the period after pneumococcal vaccination (r = -0.683, p = 0.0001). Conclusion: These results suggest that a high percentage splenectomized ?-thalassemia patients are poor responders to pneumococcal vaccination. Therefore evaluations immunity levels of pneumococcal vaccine and re-vaccination for pneumococcus are recommended in these patients.