OBJECTIVES: To describe Staphylococcus aureus infections in children with diabetes mellitus (DM). METHODS: Children with DM (cases) and S. aureus infections (2/02-6/10) were identified from a surveillance database. Patient charts were reviewed, and S. aureus isolates were characterized by molecular methods. Cases were compared to age-matched controls without DM but with CA-S. aureus skin and soft tissue infections (SSTI) using conditional logistic regression. RESULTS: Forty-seven cases were identified; 41 were matched with 123 controls. Four cases had osteomyelitis and 43 had SSTI. Mean age was 14.2 years and 63% of cases had hemoglobin (Hb) A1c levels above 10%. Cases and controls differed by gender (85% vs. 45% female, P<0.001), BMI% (median 87% vs. 72%, P=0.04), methicillin-resistant S. aureus (MRSA) infection (49% vs. 68%, P=0.04), and recurrent infections (22% vs. 4%, P=0.001). Among cases, 88% of recurrences were caused by MRSA. CONCLUSIONS: The majority of cases had poor glycemic control, more recurrences, fewer primary MRSA infections and were more likely to be female compared to a control group. Improved glycemic control may reduce the risk for infection, and decrease hospitalizations due to S. aureus infections.