Antibody-dependent enhancement (ADE) is a major concern in feline infectious peritonitis virus (FIPV) pathogenesis as it could exacerbate disease through mechanisms that extend beyond enhanced viral infection. Using a spike protein–primed feline coronavirus (FCoV) model of feline infectious peritonitis (FIP), we applied untargeted plasma metabolomics to define the metabolic landscape associated with ADE. While FIPV infection alone was characterized by altered tryptophan metabolism, depletion of pro-resolving lipid mediators, and disturbances in energy metabolism, ADE induced a distinct immunometabolic state marked by primary bile acid accumulation, elevated acylcarnitines, enhanced tryptophan–kynurenine flux, glutathione depletion, and cholesterol dysregulation. Metabolites including 3-Glc-Brass, 2-Hydroxypalmitic Acid, taurocholate, and octanoylcarnitine robustly distinguished ADE from conventional infection, highlighting profound alterations in hepatobiliary function, mitochondrial β-oxidation, and redox homeostasis. Together, these findings demonstrate that ADE drives a unique immunometabolic reprogramming rather than simply amplifying coronavirus disease severity and identify bile acid and acylcarnitine pathways as potential biomarkers and therapeutic targets for ADE-associated coronavirus pathology.