The association between nutrition and mental diseases has been extensively studied. Vitamin B12 and folic acid are the main vitamins in the development of the central nervous system. This study aimed to investigate the relationship between vitamin B12 and folic acid levels with depression and anxiety. A total of 150 patients (77 with anxiety and 73 with depression) between 18 and 79 were enrolled. The initial mood state was evaluated using Beck’s Depression Inventory-II (BDI-II) and Beck’s Anxiety Inventory (BAI) for the presence of depression and anxiety, respectively. Venous blood samples were collected after overnight fasting and vitamin B12 and folic acid levels were measured. Serum concentrations of folic acid were significantly lower in patients with depression than those with anxiety (p=0.04). Substantially higher vitamin B12 levels were described in men than females counterparts with severe depression (p=0.049). Additionally, there was a significant inverse correlation between folic acid levels and Beck’s inventory score among patients with severe depression (r=-0.250, p=0.049). Serum levels of vitamin B12 and folic acid could be used as markers that assess anxiety and depression’s therapeutic efficiency.