Alkali metals (AMs) and alkali earth metals (AEMs) affect levels and signalling of neurotransmitters, which potentially play a role in the etiology of schizophrenia (SCZ). The current case-control study aims to explore how AMs [i.e. Potassium (K), sodium (Na), rubidium (Rb), cesium (Cs)] and AEMs [i.e. magnesium (Mg), calcium (Ca), strontium (Sr), barium (Ba)] in serum could associate with SCZ. One hundred and five inpatients with SCZ and 106 age- and sex-matched healthy controls (HCs) were recruited from Weifang, China. Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) was used to evaluate serum concentrations of Na, K, Ca, Mg and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was for Rb, Cs, Sr, Ba. Subjects with SCZ had significantly higher Mg and Sr serum concentrations than HCs (20.86 vs. 19.73 μg/mL of Mg, p < 0.001; 53.14 vs. 42.26 ng/mL of Sr, p < 0.001). After adjusting for confounders, the odds ratio of Mg and Sr remain significantly higher in the SCZ group (Mg: OR = 2.538, 95% CI: 1.254-5.136, p=0.010; Sr: OR = 3.798, 95% CI: 1.769-8.153, p = 0.001). No significant differences between SCZ subjects and HCs were observed for other AMs and AEMs. Higher serum concentrations of Mg and Sr were associated with SCZ. Studies are suggested to find the related mechanisms and provide clues for pathogenesis of SCZ, which would impact prevention and treatments of SCZ.