Objective: To find the metabolomic characteristics of tumor or para-tumor tissues, and the differences in serums from papillary thyroid cancer (PTC) patients with or without lymph node metastasis. Methods: We collected serums of PTC patients with/without lymph node metastasis (SN1/SN0), tumor and adjacent tumor tissues of PTC patients with lymph node metastasis (TN1 and PN1), and without lymph node metastasis (TN0 and PN0). Metabolite detection was performed by ultra-high performance liquid chromatography combined with Q-Exactive orbitrap mass spectrometry (UPLC Q-Exactive). Results: There were 31, 15, 4 differential metabolites in the comparisons of TN1 and PN1, TN0 and PN0, SN1 and SN0, respectively. Seven uniquely increased metabolites and fourteen uniquely decreased metabolites appeared in the lymph node metastasis (TN1 and PN1) group. Meanwhile, the results indicated that four pathways were co-owned pathways in two comparisons (TN1 and PN1, TN0 and PN0), and four unique pathways presented in the lymph node metastasis (TN1 and PN1) group. Conclusions: Common or differential metabolites and metabolic pathways were detected in the lymph node metastasis and non-metastatic group, which might provide novel ways for the diagnosis and treatment of PTC.