In this study, the impacts of egg consumption on mice model of metabolic syndrome (MetS) were comparatively investigated. Mice were divided into five groups (n=8): normal diet group (ND), high-fat diet group (HFD), HFD with whole egg group (WE), HFD with free-yolk egg substitute group (YFES), and HFD with lovastatin group (Lov). Main biochemical indexes and a non-targeted lipidomic analysis were employed to insight the lipid profile changes in serum. It was revealed that WE could significantly improve serum biochemical indexes by reducing body weight, low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC), while increasing high-density lipoprotein cholesterol. YFES exhibited remarkably better performance in increasing phosphatidylglycerol and phosphatidic acids, while decreasing phosphatidylinositol than WE. A total of 50 differential lipids biomarkers tightly related to glycerophospholipids metabolism were screened out. Carnitine C18:2 and C12:1, SM (d18:0/12:0), and SM (d18:1/14:1) were significantly upregulated in YFES compared to WE. YFES reduced expression of SREBP-1c and Cpt1a, while did not affect the expression of PPAR-α. Sphingomyelin biomarkers were positively related to the TC (|r| > 0.6), while PPAR-α was negatively correlated with triglyceride and LDL-C levels. To sum up, YFES attenuated HFD-induced MetS by improving the serum phospholipids, which account for its modulation of glycerophospholipid metabolism.