Hemolytic uremic syndrome has been associated with insulin-dependent diabetes mellitus eight times in the past, while the hemolytic uremic syndrome and rhabdomyolysis association has been described once. The occurrence of both conditions in a patient with the hemolytic uremic syndrome has not been reported. In this report, we described a 28-month-old girl who presented with severe hemolytic uremic syndrome muscle weakness and elevated muscle enzymes. Later, she developed hyperglycemia and ketosis requiring initiation of insulin therapy. The current literature was reviewed, and a hypothesis for the mechanism of injury and the multisystemic nature of this syndrome is presented. In patients with the hemolytic uremic syndrome, identification of potential extrarenal involvement is important as it may determine the final outcome of this disease.