Competition horses are under pressure from a wide range of stressors putting them at higher risk of infectious disease. Ingestion of Saccharomyces cerevisiae fermentate (SCF) products have been shown to improve immunocompetence in humans and other species, and we hypothesized it would provide similar benefits for horses. Yeast fermentate contains cellular components that can bind to pathogens and stimulate host immune cells, as well as bioactive fermentation byproducts (e.g., short chain fatty acids, vitamins, antioxidants) that can augment gut and other mucosal defenses. This study aimed to evaluate the effect of SCF on mucosal immunity in young horses in training. Two-year-old Quarter Horses (mean ± SEM; initial age 22 ± 0.3 mo and BW 439 ± 3 kg) were paired by age and sex and randomly assigned to receive SCF (Diamond V, Cedar Rapids, IA; 21 g/d; n = 10) or no supplement (CON; n = 10) added to their diet (60% hay, 40% concentrate) for 60 d. Horses were exercised 4 d/wk for 30–45 min/d at light to moderate intensity. On d 57, horses were placed in individual stalls and tethered with their heads elevated 35 cm above wither height for 12 h to induce mild upper respiratory tract inflammation. Feces, whole blood, and nasopharyngeal flush (NPF) samples were obtained at study initiation and before and up to 72 h after stress induction to evaluate immune responses. Data were compared using mixed model ANOVA with time as a repeated measure. Prolonged head elevation resulted in greater ( P < 0.0001) serum cortisol and increases ( P < 0.05) in mucus, total leukocytes, neutrophils, lymphocytes, monocytes, and ratio of neutrophils to lymphocytes in NPF, indicative of an inflammatory response that was mostly resolved by h 72. A similar leukogram was observed in whole blood, though it was delayed 12 h compared with NPF. Neutrophils and lymphocytes were lower ( P < 0.05) and monocytes greater ( P < 0.05) in NPF from horses fed SCF than CON. Immunoglobulin (Ig) A in NPF exhibited a time × treatment effect ( P = 0.05) with an increased response to head elevation in SCF horses but no change in CON. Head elevation increased ( P < 0.05) IgA, IgG and IgM in feces, and fecal concentrations of IgA and IgG were greater ( P < 0.05) for CON than SCF. Serum IgA, IgG, and IgM were not affected by head elevation nor treatment. Changes in leukocytes and IgG in mucosal secretions suggest a stronger inflammatory response to head elevation in CON horses. Higher IgA in NPF from SCF horses may have helped attenuate local inflammation. Further study is needed to determine if SCF could improve other markers of disease resistance.