Background <p>Several psychiatric disorders have been associated with vitamin B12 and folic acid deficiency, such as mood disorders and obsessive–compulsive disorder (OCD). Vitamin B12 and folic acid play a crucial role in the carbon transfer metabolism that is necessary to produce serotonin. Many studies found low vitamin B12 levels, and indifferent folic acid levels in patients with OCD. More research focusing on vitamin B12 and folic acid, as well as their roles, can be beneficial to establish their association with OCD that will help in the therapeutic process. This study aimed to compare the blood levels of B12 and folic acid between a group of OCD patients and a group of healthy controls.</p> Methods <p>This study is a cross-sectional analysis of 44 Egyptian patients diagnosed with OCD compared with 44 healthy control subjects. The comparison was based on demographics, clinical parameters, and B12 and folic acid levels. The diagnosis of OCD was based on the application of the structured clinical interview for DSM-IV Axis I Disorders. The Arabic version of the Yale-Brown Obsessive–compulsive Scale (Y-BOCS) was administered to assess the severity of OCD<Emphasis Type="BoldItalic">.</Emphasis> Blood samples were collected from all participants to measure vitamin B12 and foliate levels<b>.</b></p> Results <p>Patients with OCD exhibited significantly lower vitamin B12 levels compared to controls (<i>P</i> = 0.03), however, there was no statistically significant difference in folic acid levels between patients with OCD and the control group (<i>P</i> = 0.08). A strong inverse correlation was seen between Y-BOCS scores and vitamin B12 levels (<i>P</i> = 0.04).</p> Conclusions <p>There was a statistically significant association between lower vitamin B12 levels and OCD, this important finding could be an advance in the therapeutic process in patients with OCD. These findings suggest that vitamin B12 levels may be associated with OCD severity, warranting further investigation.</p>