We report a case of severe hemolytic anemia following Mycoplasma pneumoniae infection in a 29-year-old male patient who was treated with azithromycin. Direct Coombs' test was strongly positive and the cold agglutinin titer was high, with anti-I specificity. Antimycoplasma antibody titer by complement fixation was high 1:10,240. The patient was discharged after 12 days of hospitalization in good health. He remains clinically well with no recurrence of jaundice. © 2009 by The Brazilian Journal of Infectious Diseases and Contexto Publishing. All rights reserved.