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This study evaluated the effects of probiotic and selenium co-supplementation on clinical and metabolic symptoms in patients with chronic schizophrenia. A randomized, double-blind, placebo-controlled trial was conducted among 60 people with chronic schizophrenia to receive either 8 × 10 CFU/day probiotic plus 200 μg/day selenium (n = 30) or placebo (n = 30) for 12 weeks. Probiotic and selenium co-supplementation resulted in a significant improvement in the general Positive and Negative Syndrome Scale (PANSS) score (β - 1.29; 95% CI, - 2.48, - 0.10; P = 0.03) compared with the placebo. Compared with the placebo, probiotic and selenium co-supplementation resulted in a significant elevation in total antioxidant capacity (β 91.09 mmol/L; 95% CI, 35.89, 146.30; P = 0.002) and total glutathione (β 96.50 μmol/L; 95% CI, 26.13, 166.87; P = 0.008) and a significant reduction in high-sensitivity C-reactive protein levels (β - 1.44 mg/L; 95% CI, - 2.22, - 0.66; P = 0.001). Additionally, co-supplementation significantly decreased fasting glucose (β - 7.40 mg/dL; 95% CI, - 10.15, - 4.64; P < 0.001), insulin levels (β - 1.46 μIU/mL; 95% CI, - 2.35, - 0.57; P = 0.002), and homeostasis model of assessment-insulin resistance (β - 0.51; 95% CI, - 0.72, - 0.29; P < 0.001) and a significant increase in quantitative insulin sensitivity check index (β 0.01; 95% CI, 0.006, 0.01; P < 0.001) compared with the placebo. Probiotic and selenium co-supplementation for 12 weeks to patients with chronic schizophrenia had beneficial effects on the general PANSS score and some metabolic profiles. http://www.irct.ir , identifier IRCT20170513033941N41.