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Uncontrolled inflammation is a contributing factor to many leading causes of human morbidity and mortality including atherosclerosis, cancer and diabetes. Se is an essential nutrient in the mammalian diet that has some anti-inflammatory properties and, at sufficient amounts in the diet, has been shown to be protective in various inflammatory-based disease models. More recently, Se has been shown to alter the expression of eicosanoids that orchestrate the initiation, magnitude and resolution of inflammation. Many of the health benefits of Se are thought to be due to antioxidant and redox-regulating properties of certain selenoproteins. The present review will discuss the existing evidence that supports the concept that optimal Se intake can mitigate dysfunctional inflammatory responses, in part, through the regulation of eicosanoid metabolism. The ability of selenoproteins to alter the biosynthesis of eicosanoids by reducing oxidative stress and/or by modifying redox-regulated signalling pathways also will be discussed. Based on the current literature, however, it is clear that more research is necessary to uncover the specific beneficial mechanisms behind the anti-inflammatory properties of selenoproteins and other Se metabolites, especially as related to eicosanoid biosynthesis. A better understanding of the mechanisms involved in Se-mediated regulation of host inflammatory responses may lead to the development of dietary intervention strategies that take optimal advantage of its biological potency.