Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in children, with a peak incidence at 5-14 years. Extrapulmonary manifestations occur in 20-25% of patients with M. pneumoniae infection. Most auto-antibodies that cause immune hemolytic anemia in humans are cold agglutinins. The formation of cold agglutinins is frequently observed during M. pneumoniae infections, and cold agglutinin disease usually occurs during M. pneumoniae infections. Nevertheless, severe hemolysis is exceptional. If a patient has any underlying disease related to hemolysis, it is possible to accelerate hemolysis. Hereditary spherocytosis is a common cause of hereditary hemolytic anemia resulting from red blood cell membrane defects. Hemolysis of red cells may result from corpuscular abnormalities or extracorpuscular abnormalities, such as immune or non-immune mechanisms. We report a case of hereditary spherocytosis associated with severe hemolytic anemia due to Mycoplasma pneumonia.