Simple SummaryDietary supplementation has been used in order to improve animal growth and health, and reduce the risk of disease for many years. Yeast and yeast products are a group of supplements that have broad applications in livestock production. These benefits include improving milk production, weight gain, and immunity. Recent studies suggest that yeast can have impacts beyond growth and health and may impact metabolism. Available energy is important for immune activation, and therefore any change in metabolism and energy availability may affect immune responses. This paper explores the effects of yeast on energy metabolism and how these changes may influence immune responses in cattle and swine.Nutritional supplementation has been used by livestock producers for many years in order to increase animal performance, improve animal health, and reduce negative effects associated with enteric and/or respiratory pathogens. Supplements such as yeast and yeast-based products have broad applications across many livestock production systems, including poultry, aquaculture, cattle, and swine and have been shown to benefit animal production at various stages. These benefits include improvement in milk production, weight gain and feed conversion, as well as immune function. Initial research into the mode of action for these effects has focused on stimulation of the immune system by the β-glucan fractions of yeast. However, emerging studies have revealed that some of the beneficial effects of yeast products may stem from altering metabolism, including the availability of glucose and fatty acids. These changes in metabolism, and potentially energy availability, may partially explain differences in immune function observed in yeast-supplemented livestock, as the energy demands of an activated immune system are extremely high. Thus, this paper explores the influence of yeast products on metabolism in cattle and swine, and how changes in metabolism and energy availability may contribute to improvements in immune function in supplemented animals.