Zearalenone (ZEN), a mycotoxin produced by Fusarium in food and feed, causes serious damage to the health of humans and livestock. Therefore, we compared the metabolomic profiles in the liver, serum, and urine of piglets fed a ZEN-contaminated diet using proton nuclear magnetic resonance (1H-NMR) spectroscopy. The spectra from the three different samples, treated with ZEN concentrations of 0.8 mg/kg for 4 weeks, were aligned and identified using MATLAB. The aligned data were subjected to discriminating analysis using multivariate statistical analysis and a web server for metabolite set enrichment analysis. The ZEN-exposed groups were almost separated in the three different samples. Metabolic analysis showed that 28, 29, and 20 metabolites were profiled in the liver, serum, and urine, respectively. The discriminating analysis showed that the alanine, arginine, choline, and glucose concentrations were increased in the liver. Phenylalanine and tyrosine metabolites showed high concentrations in serum, whereas valine showed a low concentration. In addition, the formate levels were increased in the ZEN-treated urine. For the integrated analysis, glucose, lactate, taurine, glycine, alanine, glutamate, glutamine, and creatine from orthogonal partial least squares discriminant analysis (OPLS-DA) were potential compounds for the discriminating analysis. In conclusion, our findings suggest that potential biomarker compounds can provide a better understanding on how ZEN contaminated feed in swine affects the liver, serum, and urine.