Numerous essential metal elements (EMEs) are necessary to maintain the proper function of human body. In this case-control study, we investigated the associations of 11 EMEs [Calcium (Ca), potassium (K), magnesium (Mg), sodium (Na), manganese (Mn), selenium (Se), cobalt (Co), Molybdenum (Mo), copper (Cu), zinc (Zn), and iron (Fe)] in serum with the risk of schizophrenia. We recruited first-episode and drug-naïve schizophrenic patients (cases = 99) and age-sex-matched normal subjects (controls = 99) from Tangshan, Hebei Province, China. The 11 EMEs in serum from cases and controls were quantified by inductively coupled plasma atomic emission spectrometry and inductively coupled plasma mass spectrometry. We observed that a higher level of Mn (OR = 2.390; 95%CI: 1.504-3.796) and lower levels of Ca (OR = 0.939; 95%CI: 0.890-0.990), Mg (OR = 0.806; 95%CI: 0.669-0.972), Na (OR = 0.995; 95%CI: 0.993-0.998), and Se (OR = 0.954; 95%CI: 0.937-0.972) were associated with an elevated risk of schizophrenia. Dose-response relationships between serum EME concentrations and the risk of schizophrenia were observed in most of the schizophrenia-associated EMEs. Moreover, the serum concentrations of these schizophrenia-associated EMEs in patients were correlated with the severity of their clinical symptoms. Significant correlations were found between EMEs and biomarkers associated with schizophrenia related to metabolic and oxidative stress. This study suggested that the concentration and profile of EMEs were different between schizophrenic patients and normal controls and revealed potential metabolisms associated with EMEs and schizophrenia, suggesting EMEs might act as biomarkers of schizophrenia to improve the current situation of diagnosis and treatment.