Previous studies have indicated that schizophrenia is linked to abnormal lipid metabolism. Free fatty acids (FFAs) in peripheral blood can reflect the status of lipid metabolism in human body. The purpose of this study was to scan the FFA pattern and elucidate the characteristics of lipid metabolic abnormality in schizophrenia patients. One hundred and ten patients with schizophrenia (SCZs) and 109 healthy controls (HCs) were included in the study and divided into a discovery set and a validation set. Forty-seven serum FFAs were detected by UPLC-QTOF-MS and 39 of them were absolutely quantified by establishing standard curves. Monounsaturated fatty acids (MUFAs) and ω-6 polyunsaturated fatty acids (ω-6 PUFAs) were significantly increased in SCZs compared with HCs. Desaturation from saturated fatty acids to MUFAs and β-oxidation were enhanced, as estimated by the ratios of products to precursors. These results suggest that lipolysis and β-oxidation are upregulated in SCZ, presumably resulting from insufficient brain energy supply.