Objective To search the different metabolites related with Kaschin-Beck disease (KBD) in serum of children with KBD. Methods Among the children aged 7 - 15 years old in the KBD areas in Qinghai Province,by the X ray and clinical examination,56 KBD patients(case group) and 51 non-KBD children (internal control group)were selected.Meantime,in non-KBD areas where the economic level and living habits was similar to that of the KBD areas, 50 healthy children were selected as external control group. Children's fasting blood samples were collected, and the metabolic profile in serum was determined by ultra performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC/QTOF-MS) technique. Combined with multivariate statistical analysis, database searching was applied to explore and search the different endogenic metabolites associated with KBD, to find biologically targeted makers. Results There were 1 384 serum metabolites with significant differences in case group, internal control group and external control group, 670 serum metabolites with significant differences in case group and external control group, including 25 KBD related endogenous differential metabolites. Among them, the relative contents of kynurenic acid and arachidonic acid in case group were higher than that of external control group, and the relative contents of N-α-acetylarginine, 6-hydroxymelatonin and sphinganine in case group were lower than that of external control group (P < 0.05). Conclusions The serum metabolic profile of children in KBD areas and children in non-KBD areas is significantly different. N-α-acetylarginine, kynurenic acid, 6-hydroxymelatonin, sphinganine and arachidonic acid are more closely related with KBD,and they can be considered as a clue in screening KBD biomarkers.