Technical Abstract: Effective nutritional approaches to counteract the negative effects of stress would both improve human health and provide food animal producers with useful alternatives to antibiotics. In this study, turkeys were fed a standard diet or the same diet supplemented with yeast extract (Alphamune™, YE), to determine if YE would improve disease resistance in a stress model. At 16 weeks of age half of the birds were exposed to a bacterial challenge using coarse spray of the pen environment. A subset of control and challenged birds was also treated with dexamethasone (Dex) prior to challenge (Dex/challenge). At 18 weeks, another subset was subjected to a 12 h transport stress protocol (Challenge/transport). All birds were bled and necropsied the morning after transport. The numbers and proportions of blood cells and the heterophil oxidative burst activity (OBA) were determined. Serum corticosterone (Cort) levels of male birds were measured using a commercial ELISA. Body weight and gain were increased by YE during week 1(P < 0.0001). 3. YE decreased mortality and bacterial isolation following Dex/challenge only in females (P = 0.004). Cort levels in male turkeys were decreased by YE (P = 0.02) and Dex treatment (P < 0.0001). OBA was higher in males and in birds fed YE (P < 0.0001) and was decreased by challenge and transport (P < 0.0001). 4. These results suggest there may be gender differences in the turkey stress response and that dietary YE has potential for modulating the impact of stress on innate immunity of turkeys.