The neonatal bovine immune system is characterized as being immunonaїve at birth. Lysophosphatidylcholine (LPC) is an immunomodulator in non-ruminants that functions by enhancing bactericidal mechanisms of immune cells. Because the role of LPC in ruminants had not received prior attention, our objectives were to (1) determine whether LPC modulates neonatal bovine neutrophil oxidative burst, cytokine release, and Escherichia coli (E. coli) killing and (2) investigate the effects of subcutaneous (s.c.) and dietary LPC administration on immunity and growth in calves. For study 1, neutrophils were isolated from peripheral blood of pre-weaned Holstein heifer calves. The effects of LPC were evaluated on hydrogen peroxide (H2O2) production, tumor necrosis factor-α (TNFα) and interleukin (IL)-6 secretion, and Escherichia coli killing. We observed that LPC-18:0 enhanced phorbol myristate acetate-stimulated H2O2 production, potentiated the ability of lipopolysaccharide to stimulate TNFα and IL-6 secretion, and enhanced neutrophil-mediated E. coli killing. For study 2, forty-six Holstein heifer calves were randomly assigned to 1 of 4 treatments: a milk replacer diet unsupplemented with lecithin in the absence (CON; n=11) or presence of s.c. administered mixed (mLPC; 69% LPC-16:0, 25% LPC-18:0, 6% other; n = 11) or pure (pLPC; 99% LPC-18:0; n = 11) LPC, or a milk replacer diet supplemented with 3% lecithin enriched in lysophospholipids containing LPC in the absence of s.c. administered LPC (LYSO; n = 10). Starter grain and water were provided. Body measurements and clinical observations were recorded, and blood samples were collected. Rectal temperatures were higher in calves treated with mLPC or pLPC during administration, relative to CON. Calves provided mLPC experienced lower body weight and average daily gain post-weaning, relative to CON. Calves receiving mLPC displayed increased serum aspartate aminotransferase, γ-glutamyltransferase, and glutamate dehydrogenase concentrations and a tendency for increased white blood cell counts during wk 3 of life, relative to CON. Plasma concentrations of SAA were significantly higher in mLPC and pLPC calves, relative to CON calves immediately prior to and following the final s.c. injection. We conclude that LPC enhanced bactericidal mechanisms of bovine neutrophils, and the s.c. injection of saturated LPC to healthy calves induced an acute febrile response, modified measures of liver and immune function, and impaired growth.