|Abstract:||Coccidiosis is an intestinal parasitic disease caused by protozoans of the genus Eimeria and substantially impacts the poultry industry economically worldwide by diminishing animal growth. The prophylactic use of anticoccidial drugs in order to ameliorate the detrimental effects of an Eimeria infection has been the most successful control measure in broilers. However, due to an increase in resistance to anticoccidial drugs and a growing public concern for the development of resistant microorganisms, dietary intervention as a nutritional alternative to antibiotics and anticoccidial drugs have become of specific interest to combat coccidiosis in broilers. Because of this, an experiment was conducted to determine if dietary Yucca-derived saponin supplementation could mitigate the immune and growth responses of broilers during a mixed coccidian challenge. Dietary treatments were corn-soybean meal-based and included: 1) control diet + sham-inoculated (Ucon), 2) control diet + Eimeria oocyst challenge (Icon), 3) control diet with 250 mg/kg Yucca-derived saponin product + Eimeria oocyst challenge (ISap250), and 4) control diet with 500 mg/kg of Yucca-derived saponin product + Eimeria oocyst challenge (ISap500). Growth performance, oocyst shedding, histopathological morphometrics and lesion scoring, differential blood cell counts, immunophenotyping of cecal-derived T-cell profiles, and intestinal inflammatory cytokine gene expression were evaluated in broilers inoculated with a mixture of E. acervulina, E. maxima, and E. tenella oocysts. The birds challenged with Eimeria showed clear signs of a successful infection, as evidenced by oocyst counts of excreta samples collected from each pen. The birds challenged orally with the Eimeria mixture displayed a reduction in growth compared with birds not challenged with the Eimeria mixture, but there was no detectable difference due to dietary treatment when comparing amongst infected birds alone. Histopathological analysis identified a treatment effect for mucosal thickness in the jejunum, where infected birds fed an inclusion rate of 250 mg/kg of diet of saponin supplementation and the un-infected control diet birds were not significantly different from each other. Histopathological lesion scoring exhibited no detectable differences due to dietary treatment within the Eimeria-infected groups. Seven days following Eimeria inoculation, lymphocytes as a percentage of white blood cells were elevated in all infected treatment groups, but birds fed saponin supplementation at 250 mg/kg of diet did not differ from the un-infected control diet birds. Saponin supplementation in conjunction with an Eimeria challenge had no measureable effect on cecal-derived T-cell profiles. Expression of cecal and duodenal IFN-γ increased with infection when compared to the sham-inoculated birds. Inoculation with Eimeria also increased expression of IL-1β, but saponin supplementation at 250 mg/kg and 500 mg/kg of diet ameliorated IL-1β expression in the cecal tonsils and duodenum to levels not different from sham-inoculated birds. Overall, this research demonstrates that dietary intervention in the form of saponin supplementation may serve as an effective strategy in mitigating the resulting inflammatory response following exposure to Eimeria in broilers as evidenced by lymphocyte responses, changes in intestinal structure, and alterations in cecal and duodenal inflammatory cytokine mRNA expression.