The 2009 H1N1 Influenza virus was the first infectious pandemic of the 21(st) century which spread rapidly throughout the world. High-risk groups, such as diabetics, suffered more and showed higher hospital admission and death rates due to this virus. Patients with diabetes mellitus (DM) may develop the fulminant picture of their disease after being infected with influenza. From June to December 2009 at Nemazee Hospital, affiliated with Shiraz University of Medical Sciences, two patients with diabetic ketoacidosis (DKA) were admitted. The H1N1 influenza virus triggered DKA and its complications in these patients. Both patients were female, of ages 16 and 40 years. When admitted, they had signs of influenza-like illness (ILI), tachypnea, laboratory confirmation of acidosis, and high blood sugar levels. The 2009 H1N1 influenza viral RNA was detected in their nasopharyngeal specimens by real time polymerase chain reaction (RT-PCR). Both patients received oseltamivir, but eventually both died. This was the first report of an association between DKA and H1N1 influenza in Iran. Conclusively, rapid diagnosis of influenza by RT-PCR and early treatment with oseltamivir should be considered in diabetics and/or DKA patients with flu-like symptoms.