Objective To explore the correlation between unipolar depression， bipolar depression， schizophrenia and one carbon metabolizing nutrients， so as to provide clues for exploring the mechanism of different diseases and provide evidence for adjuvant therapy. Methods Inpatients in Beijing Anding Hospital Affiliated to Capital Medical University from January 2013 to December 2019 were selected as the research objects. A total of 390 patients with unipolar depression， 390 patients with bipolar depression and 865 patients with schizophrenia were included. General demographic data and one-carbon metabolizing nutrients （folic acid， vitamin B12， homocysteine） were compared among the three groups. Multiple Logistic regression analysis was used to control confounding factors and to clarify the correlation between the three diseases and one carbon metabolizing nutrient. Results Compared with unipolar depression and bipolar depression group， the level of vitamin B12 in schizophrenia patients was lower［438.5 （322.3， 581.3） pg/ml vs 449.9 （345.4， 613.3）pg/ml vs 376.9 （280.3， 505.3）pg/ml］， the level of homocysteine was higher［14.3 （11.5， 18.7） μmol/L vs 14.0 （11.6， 18.3）μmol/L vs 15.4 （12.4， 22.1）μmol/L］， the incidence rate of vitamin B12 deficiency was higher ［6.2% （24/390） vs 4.9%（19/390）vs 9.5%（82/865）］， and hyperhomocysteinemia was higher ［44.9%（175/390） vs 41.8% （163/390） vs 51.9%（449/865）］， and all differences were statistically significant （all P ＜ 0.05）. There was no significant difference in the distribution of folate level and folate deficiency among all groups （P＞0.05）. Multiple Logistic regression analysis showed that vitamin B12 level （OR=0.998， 95%CI=0.998-0.999） was the risk factors of schizophrenia （P＜ 0.05）. There was no significant difference in the levels of one-carbon metabolizing nutrients between unipolar depression and bipolar depression group （P＞ 0.05）. Conclusions Compared with unipolar depression and bipolar depression patients， schizophrenia patients have more obvious one-carbon metabolic nutrient deficiency， lower vitamin B12 level and higher homocysteine level. There was no significant difference in the levels of one-carbon metabolizing nutrients between unipolar depression and bipolar depression patients.