Fulminant type 1 diabetes (FT1DM) is a relatively new clinical entity featured by acute destruction of pancreatic beta cells. Clinical consequences of FT1DM could be fatal when timely medications are not provided, suggesting the particular importance of rapid and accurate diagnosis. Here we report a serum metabonomics study of FT1DM patients, together with healthy control subjects (NC), type 2 diabetes (T2DM), classic type 1 diabetes (T1DM), and diabetic ketoacidosis (DKA) patients, with the aim of discovering metabolic markers associated with FT1DM. A total of 79 subjects were enrolled (22 NC, 22 T1DM, 22 T2DM, 8 DKA and 5 FT1DM) and the serum metabolic profiling of fasting blood samples was performed using gas chromatography time-of-flight mass spectrometry (GC-TOFMS) coupled with multivariate and univariate statistical analyses. Serum metabolites differentially expressed in FT1DM relative to NC, or to T2DM, T1DM and DKA were identified. Three metabolite markers, 5-oxoproline, glutamate, and homocysteine, were significantly altered among FT1DM, T2DM, T1DM, and DKA. In addition, the three metabolite markers, 5-oxoproline, glutamate, and homocysteine, presented similar patterns of distribution across groups. The results showed that the metabolic signatures of FT1DM identified in this study could be of potential clinical significance for the accurate diagnosis of FT1DM.