Egg-yolk based supplements have demonstrated biological effects. We have developed a novel processed egg-yolk (PEY) complement, and we have tested whether it has inflammation modulatory properties. These were evaluated in a lipopolysaccharide (LPS)-challenge in 1-month male rats by in vivo circulating cytokine profiles measured by multiplexing techniques. Cell culture was used to explore ex vivo properties of derived serum samples. We explored growth factor composition, and mass-spectrometry metabolome and lipidome analyses of PEY to characterize it. PEY significantly prevented LPS-induced increase in IL-1 β, TNF-α, and MCP-1. Further, serum from PEY-treated animals abrogated LPS-induced iNOS build-up of the Raw 264.7 macrophage-like cell line. Immunochemical analyses demonstrated increased concentrations of insulin-like growth factor 1 (IGF-1), connective tissue growth factor (CTGF), and platelet-derived growth factor (PDGF) in the extract. PEY vs. egg-yolk comparative metabolomic analyses showed significative differences in the concentrations of at least 140 molecules, and in 357 in the lipidomic analyses, demonstrating the complexity of PEY. Globally, PEY acts as an orally-bioavailable immunomodulatory extract that may be of interest in those conditions associated with disarranged inflammation, such as inflammaging.