Background: The contribution of B12 and folate deficiencies to pathophysiology of psychiatric illnesses is well known worldwide, however it was not evaluated in Sudanese psychiatric patients. Aim: To assess the association between the neuropsychiatric syndromes and the levels of both vitamin B12 and folic acid in Sudanese psychiatric patients. Materials and Methods: The study involved a test group of 100 psychiatric patients and an age/gender matched control group of 100 subjects with no past history of psychiatric illness. Laboratory investigations, including complete blood count (CBC), serum vitamin B12 and folate concentrations were done to all studied subjects. Significance of the difference in the means of the studied variables and the association between psychiatric illnesses and both B12 or folic acid deficiencies were assessed using appropriate statistical tests. Results: Most of hematological indices were significantly less in psychiatric patients, although their means were within normal range. The serum concentrations of vitamin B12 in the psychiatric patients (M±SD = 527.9 ± 305. 8 pg/ml) were significantly lower compared with the control group (M±SD = 590.5± 186.1 pg/ml, P = 0.001). There was significant association between B12 deficiency and psychiatric illnesses (P = 0.014). Six percent of the psychiatric patients were suffering from B12 deficiency while none the control group was suffering from the same deficiency. The serum concentrations of folic acid were comparable in both studied groups (M±SD = 7.2 ± 1.7 ng/ml, 7.2 ± 2.6 ng/ml in the control and test groups respectively, P > 0.05). There was no folic acid deficiency in both test and control groups. Conclusion: There was association between vitamin B12, but not folic acid, deficiency and psychiatric diseases in studied Sudanese subjects. Most of the hematological indices were significantly less in psychiatric patients, although their means were within normal range. The significantly lower levels of vitamin B12 deficiency were not associated with megaloblastic changes.