Hemolytic uremic syndrome (HUS) in associated with infections of neuraminidase-producing Streptococcus pnumoniae was rarely reported in the literature. We report two infants with proven peumococcal meningitis associated with anemia, thrombocytopenia, renal failure, and T-antigen activation characteristic of neuraminidase activity. This supports a common pathogenesis in HUS following infection of neuraminidase-producing strains of S. pneumoniae. One infant complicated with status epilepticus died, and the other infant survived without sequelae. We recommend that neuraminidase production should be considered in case of pneumococcal meningitis associated with anemia and thrombocytopenia without diffuse bleeding tendency. Early recognition of HUS associated S. pneumoniae neuraminidase production is vital. The use of compatible washed red blood cells, meticulous supportive care and appropriate use of dialysis will improve survival.