Infection leads to profound alterations in whole-body metabolism, which is characterized by marked acceleration of glucose, fat and protein, and amino acid flux. One of the complications of infection, especially in the nutritionally supported setting, is hyperglycemia. The hyperglycemia is caused by peripheral insulin resistance and alterations in hepatic glucose metabolism. The defects in hepatic glucose metabolism include overproduction of glucose and a failure of the liver to appropriately adapt when nutritional support is administered. Investigators have suggested that multiple factors contribute to the observed defects. In this review, I focus primarily on alterations in carbohydrate metabolism, examining both the metabolic response to infection and inflammatory stress, the role of the accompanying neuroendocrine and inflammatory responses in the metabolic response, and the interaction between the endocrine response to infection and nutritional support.