Clinical definition and appropriate management of anaphylaxis is a clinical challenge because there is large variability in presenting clinical signs and symptoms. Monitoring of the metabolic status of anaphylaxis may be helpful in understanding its pathophysiological processes and diagnosis. The purpose of this study was to conduct GC-MS serum metabolic profiling of anaphylaxis animal models and search for potential biomarkers of anaphylaxis. Thirty-six guinea pigs were randomly divided into an ovalbumin group (n = 12), a cattle albumin group (n = 12), and a control group (n = 12). The IgE level in the serum of the guinea pigs was evaluated by use of ELISA kits and the major metabolic changes in serum were detected by gas chromatography-mass spectrometry. Typical clinical symptoms appeared after the animals had been challenged with ovalbumin or cattle albumin. The IgE levels in serum of both model groups were significantly higher than those of the control group. Clustering trend of the three groups based on variables was observed and nine out of 858 metabolomic features were found to be significantly different between control group and model groups. Among the nine features, six features were tentatively identified as metabolites related to energy metabolism and signal transduction in anaphylaxis. In conclusion, GC-MS-based metabolic profiling analysis might be an effective auxiliary tool for investigation of anaphylaxis.