The change in the plasma proteome in chicken (Gallus gallus) challenged with lipopolysaccharide (endotoxin) derived from E. coli was determined by relative quantitation using a TMT label-based approach. This study provides insights into different factors contributing to innate immune response to experimental infection during 72 hours with special emphasis on acute phase proteins (APPs). Apart from APPs, several pathways endopeptidase activation and vasoconstriction were found to be significant.