Lipopolysaccharides (LPS) are cell wall components of gram-negative bacteria and endotoxins that cause inflammation and sickness in vertebrate animals. Our objective to identify the plasma proteomic changes in an avian model of inflammation. Chickens were treated with either saline or LPS and the blood was collected 24 hours after injection. The pooled plasma samples were depleted of high abundant proteins, analyzed by Matrix assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) and liquid chromatography–tandem mass spectrometry (LC-MS/MS). MALDI-TOF analyses showed an increase in fibrinogen beta derived peptide and decrease in apolipoprotein AII- isoform X1 derived peptide in LPS samples. Label free quantitation of LC-MS/MS spectra revealed an increase in alpha-1 acid glycoprotein, chemokine-CCLI10, and cathelicidin-2 and decrease in interferon stimulated gene-12-2 in the LPS group. These differentially expressed proteins are associated with inflammation, cytokines, immunomodulation, and defense which are useful as candidate biomarkers of infection and inflammation.