Mycoplasma pneumoniae (M. pneumoniae) is a common cause of community acquired pneumonia and although most cases are mild, complications sometimes occur. Cold agglutinin hemolysis is a known complication of M. pneumoniae infection, and usually presents as a mild and transient hemolysis. Here we present a case of infection with M. pneumoniae in a 64-year-old male that caused life threatening hemolysis that required multiple blood transfusions. The patient also presented with acute kidney failure and a marked leukemoid reaction and thrombocytosis. This is a very rare combination of symptoms that could have led the clinicians to suspect a more virulent etiology than M. pneumoniae, thereby delaying adequate antibiotic treatment.