Dairy cattle are susceptible to increased incidence and severity of both metabolic and infectious diseases during the periparturient period. Health problems occurring around the time of parturition are especially problematic because they greatly affect the productive efficiency of cows in the ensuing lactation. A major contributing factor to increased health disorders is alterations in bovine immune mechanisms. Indeed, uncontrolled inflammation is a major contributing factor and a common link among several economically important diseases including mastitis, retained placenta, metritis, displaced abomasum, and ketosis. The nutritional status of dairy cows and the metabolism of specific nutrients are critical regulators of immune cell function. There is now a greater appreciation that certain mediators of the immune system also can have a reciprocal impact on the metabolism of nutrients. Thus, any disturbances in nutritional or immunological homeostasis can provide deleterious feedback loops that can further enhance health disorders, increase production losses, and decrease the availability of safe and nutritious foods for a growing global population. This review will discuss the complex interactions between nutrient metabolism and immune functions in periparturient dairy cattle. Details of how either deficiencies or overexposure to macro- and micronutrients can contribute to immune dysfunction and the subsequent development of health disorders will be presented. Specifically, the ways in which altered nutrient metabolism and oxidative stress can interact to initiate and promote uncontrolled inflammatory responses in transition cows will be discussed. Understanding more about the underlying causes of dysfunctional inflammatory responses may facilitate the design of nutritional regimens that will reduce disease susceptibility in early lactation cows. Given the critical role that nutrition plays in supporting all immune functions, nutritional-based management strategies should have a central position in any disease prevention program.