Objective To explore the association between oxidative stress markers and niacin sensitivity in male patients with chronic schizophrenia. Methods A cross-sectional study was conducted.From January to October 2020， 80 male patients with chronic schizophrenia admitted to the Psychiatric Hospital of Lianyungang were selected as patient group， and 40 healthy individuals matched in age， gender， body mass index （BMI） and so on were recruited as control group in Lianyungang during the same period. Two groups of general and clinical data were collected， and Positive and Negative Syndrome Scale （PANSS） was used to evaluate psychiatric symptoms of patient group. The niacin skin reaction test was implemented in patients and control group， and the patients were divided into niacin low reaction group （n=47） and niacin high reaction group （n=33） based on the niacin reaction score of the niacin solution concentration of 0.01 mol/L， 10 minutes， and incomplete skin erythema. Biomarkers related to oxidative stress and antioxidant capacity were measured in plasma and serum. Pearson correlation and binomial Logistic regression were used for data analysis. Results There were no statistically significant differences in age， education level， BMI， smoking， and serum nitric oxide （NO） and vitamin C between patient group and control group （all P＞ 0.05）. Skin niacin response scores， total nitric oxide synthase （TNOS）， constitutive nitric oxide synthase （cNOS）， inducible nitric oxide synthase （iNOS）， total antioxidant capacity （TAC）， and vitamin E of patient group were lower than that of control group， and the differences were statistically significant （all P＜ 0.01）. There was no association between TNOS， cNOS， iNOS， TAC， vitamin E and the total score and sub-scale scores of PANSS， and the differences were not statistically significant （all P＞ 0.05）. There was no statistically significant difference in age， education level， BMI， smoking， serum NO and vitamin C between niacin low reaction group， niacin high reaction group， and control group （all P＞ 0.05）. The differences in TNOS， cNOS， iNOS， TAC， and vitamin E among the three groups were statistically significant （all P ＜ 0.01）. There was no statistically significant difference between niacin low reaction group and niacin high reaction group in terms of chlorpromazine equivalent dose， disease duration， and onset age （all P ＞ 0.05）. Bonferroni results showed that TNOS of niacin low reaction group （P ＜ 0.001） and niacin high reaction group （P=0.002） were lower than that of control group. The difference in iNOS between niacin low reaction group and control group was statistically significant （P＜0.001）. cNOS activity of niacin low reaction group and niacin high reaction group were lower than that of control group （P＜ 0.001）. There were statistically significant differences in TAC between niacin low reaction group and niacin high reaction group （P＜ 0.001）， niacin low reaction group and control group （P=0.041）， and niacin high reaction group and control group （P=0.003）. Logistic regression analysis showed that after controlling for age， education level， BMI， smoking， disease duration， onset age， and chlorpromazine equivalent dose， TAC was a risk factor for skin niacin reaction in male patients with chronic schizophrenia， and the differences were statistically significant ［OR=1.023， 95%CI：1.012-1.034， P ＜ 0.001］. Conclusions Male patients with chronic schizophrenia exhibit abnormal oxidative stress and niacin skin reaction， suggesting that oxidative stress and niacin skin reaction may play a role in the pathological and physiological mechanisms of schizophrenia.