The objectives were to evaluate the effects of differential supplementation of Ca salts (CS) of fatty acids (FA) on plasma acute phase proteins and both FA composition and function (i.e., activity and cytokine production) of neutrophils, during the peripartum and breeding periods. Holstein cows were assigned randomly to receive either CS of palm (PO) or safflower (SO) oils from 30 d prepartum until 35 d postpartum (dpp) and CS of PO or fish oil (FO) from 35 to 160 dpp. Supplementation of CS of FA was at 1.5% of dietary dry matter. Cows (n=32) were sampled three times weekly from parturition to 35 dpp for analyses of plasma concentrations of haptoglobin and fibrinogen. Cows (n=47) were sampled for neutrophil phagocytic and oxidative burst activities toward Escherichia coli and Staphylococcus aureus, and neutrophil abundances of L-selectin and β(2)-integrin assessed by flow cytometry at 32 d prepartum, within 7h after parturition, and 4 and 7 dpp. Profiles of FA in neutrophils and cytokine production (i.e., tumor necrosis factor alpha, TNF-α, and IL-1β) were assessed prepartum (n=14), 35 (PO vs. SO; n=26) and 85 dpp (PO vs. FO; n=28). Plasma concentrations of haptoglobin and fibrinogen were greater for cows fed SO compared with PO. The percentage of neutrophils with phagocytic and oxidative burst activities was not affected by transition diets, but activities per neutrophil were greater in SO compared with PO diets at 4 (phagocytosis and oxidative burst) and 7 dpp (oxidative burst). Neutrophil abundance of L-selectin, but not β(2)-integrin, was greater in SO compared with PO at 4 and 7 dpp. Neutrophil productions of TNF-α and IL-1β were increased at 35 dpp in SO compared with PO diets, but production of TNF-α was attenuated in FO compared with PO at 85 dpp. Neutrophil ratios of n-6:n-3 FA were greater at 35 dpp in the SO diet and less at 85 dpp in FO compared with PO diets. In conclusion, cows supplemented with CS of SO had improved innate immunity (i.e., acute phase response and neutrophil function) to better cope with the bacterial challenges in the postpartum period. Conversely, CS of FO attenuated neutrophil cytokine production.