Abstract Understanding the impacts of nutrients in a species-specific manner has both practical and academic benefits for improving animal health. Therefore, species-specific animal models and research reagents are crucial to understanding molecular and physiological pathways. However, limitations in repeatable, descriptive models, sample size, and the ethics of companion animal research result in often needing to make inferences from human, murine, and other related immunology and nutrition research models. Recent companion animal work has focused on the impact of key nutrients in animal diets, including fat-soluble vitamins D, and E, omega-3 polyunsaturated fatty acids (PUFA), overall amino acid and energy balance over the lifespan, minerals including zinc and selenium, and feed additives such as probiotics and beta glucans. The selected research model, samples able to be collected, and available reagents for sample analysis will impact potential outcomes and inferences made from the data, including both acute to chronic impacts. From a theoretical standpoint, the balance between nutrient supplementation and impact includes understanding nutrients and responses of a model system in both deficiency and therapeutic level settings. For example, when supplementing Vitamin D, Vitamin E, or omega-3 polyunsaturated fatty acids, inclusion above currently recommended levels may optimize immune function, such as pathogen clearance, improved vaccine titer responses, or reduce inflammation. For other nutrients associated with immunomodulation such as zinc, additional chronic pharmacological supplementation may inhibit certain aspects of immune function, much like a deficiency scenario. Overstimulation of the immune system through nutrient supplementation may also impact the necessary modulation and repair roles that immune cells such as macrophages play in wound healing and anti-inflammatory responses. Continued work in nutritional immunology will further enhance our understanding of the power of nutrition and diet to improve health in companion animals.