Splenectomy is a safe and effective procedure in the refractory or chronic immune thrombocytopenia (ITP) patients. Overwhelming post-splenectomy infection (OPSI) is rare but fatal. The lifetime risk of post-splenectomy patients to develop an OPSI with encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae or Neisseria meningitidis) is about 1-5% and the mortality is reported more than 50% in 48 hours. Though vaccination against encapsulated bacteria cannot prevent all infection, vaccination is essential for the patients. We report a case of OPSI in a 12-year-old post-splenectomy boy who was vaccinated pneumococcal polysaccharide 7-valent against pneumococcus (Streptococcus pneumoniae) 2 months before splenectomy.