Health benefits of omega-3 (n-3) fatty acids (FA) are well known. Thus, the livestock industry has been using fishmeal (FM), rich in n-3 FA, to produce value added products. We hypothesize that FM supplementation will impact livestock health. Forty pregnant ewes were supplemented with rumen protected; soybean meal (SBM) rich in n-6 FA, or FM. During late gestation, ewes were challenged i.v. with lipospolysaccharide (LPS) to assess neuroendocrine and acute phase responses. During lactation, ewes were first sensitized i.m. to assess innate immune response and later, their acquired immune response was assessed by cutaneous hypersensitivity response (CHR). Basal haptoglobin levels were higher in SBM ewes than FM ewes (p<0.01), and they responded differently over time. The CHR to HEWL was higher in SBM ewes than FM ewes. These results suggest that n-3-rich supplements impact innate and acquired immune response of sheep, and the implications of this immunomodulation warrant further investigation.