Infectious complications in the intensive care unit (ICU) are classically identified when an elevated temperature triggers obtaining cultures. Elevated temperature, however, is a nonspecific marker of infection and may occur well into the course of the infection. The goal of this study was to evaluate whether escalating insulin demands may serve as an earlier marker for infection. A retrospective review of a prospective database from a trauma ICU over a 6-month period was done for all patients who developed infection while in the ICU. All patients in the ICU are placed at admission on an intensive insulin protocol with target blood glucose levels between 80 and 110 mg/dL. Data were collected on infection, insulin needs, blood glucose levels, temperature, white blood cell count, and antibiotic use. Twenty-four infections were identified, with 16 pneumonias, four bloodstream infections, and four urinary tract infections. Twelve of the 24 patients had increasing insulin needs in the 3 days preceding their infection diagnosis, with nine of the 12 requiring continued escalation of insulin needs from preinfection Day 3 to 2 to 1 (D3, D2, D1). In five of the 12 patients, the escalation of insulin dose preceded the elevated temperature, and in three of the 12 patients, the escalation preceded elevation of the white blood cell count above 12. For all 24 patients, the average insulin dose increased steadily, from 1.8 U/hr on D3 preinfection to 2.5 U/hr D2 and 3.1 U/hr D1. Infection does seem to be preceded by escalating insulin demands in many patients. A prospective study to evaluate the value of increased insulin demand as a marker for developing infection is warranted.