The effects of feeding fish meal to livestock have not been investigated sufficiently. To gain a broader understanding of fish meal omega fetty acid immunomodulation, different aspects of immune function were investigated. A systemic LPS endotoxin challenge, was carried out to model a systemic Gram-negative bacterial infection, and the innate immune and HPA (stress)-axis responses were assessed during late pregnancy. An antigen, HEWL, and hapten, DNCB, sensitization and challenge study was also performed to assess the innate acute phase protein response (haptoglobin) and acquired immune response (antibody and dermal hypersensitivity response) during lactation. Finally, an intramammary challenge was performed during lactation using LTA to model localized Gram-positive bacterial intramammary infection. The objectives of this study were to assess and compare local and systemic aspects of the innate and acquired immune response in pregnant and lactating ewes fed either a rumen protected fish meal (omega-3) or rumen protected soybean meal (omega-6) supplemented diet.