Technical Abstract: Stress can lead to changes in the immune response resulting in both increased and decreased resistance to opportunistic bacterial pathogens. Growth-promoting antibiotics have been a major tool in modulating host-pathogen interactions and limiting clinical and sub-clinical bacterial infection in confined animal production. Regulatory pressures to limit antibiotic use in poultry production and recent international marketing agreements that prohibit treating poultry with antibiotics have limited the disease-fighting tools available to poultry and livestock producers, particularly in Europe. There is a need to evaluate potential antibiotic alternatives to improve both production and disease resistance in high intensity food animal production. Nutritional approaches to counteract the debilitating effects of stress and infection may provide producers with useful alternatives to antibiotics. Improving disease resistance in food animals, particularly in the absence of antibiotic treatment, is a key strategy in the effort to increase food safety. ARS research has demonstrated the efficacy of several nutritional immunomodulators, including vitamin D3 and yeast cell wall products, to protect against bacterial infection due to stress and challenge with opportunistic pathogens. These studies also provide an animal model for testing the efficacy of nutritional strategies that may affect the response to stress and related infection in humans