Schizophrenia is a severe mental disorder with a lifetime risk of approximately 1%, characterized by positive and negative symptoms and cognitive deficits. It has been assumed that schizophrenia is caused by environmental and genetic factors, and their complicated interactions. However, detailed mechanisms of schizophrenia pathophysiology, in particular in terms of metabolomics pathways, still remain unknown. Some clinical studies reported altered metabolism of lipids and serine in bloods of schizophrenia patients. Sphingolipids are lipids synthesized from serine, and important mediators involved in regulation of various functions such as neural functions, apoptosis, immune responses. Recently, it was reported that sphingolipid levels were changed in postmortem brains, erythrocytes and skin from schizophrenia patients. To investigate the role of sphingolipids in schizophrenia pathology, we analyzed sphingolipids of postmortem brains (region: Brodmann area 8 and corpus callosum) from patients with schizophrenia, major depressive disorder and bipolar disorder. Our mass spectrometry-based lipid analysis detected a lower content of sphingosine-1-phosphate (S1P) in the corpus callosum of schizophrenia patients when compared to controls. To search for an underling mechanism, we examined expression levels of relevant genes, and found that genes for S1P-degrading enzymes showed trends of upregulation in the corpus callosum of schizophrenia, and the expression levels of genes for S1P receptors were increased. From these findings, it was suggested that dysregulation of sphingolipid-mediated functions might underlie schizophrenia pathophysiology.