Vitamin B12 can lead to neurological deficits. We assessed whether the mean corpuscular volume (MCV) could be a sufficiently sensitive measurement for abnormal serum methylmalonic Acid (MMA) and total plasma homocysteine (tHCY) (biomarkers of vitamin B12 or folate deficiency) and if so, at what cutoff value. A total of 26,397 participants (12,730 males and 13,667 females) were included in the analysis. Weighted analysis was performed using NHANES data to calculate crude/adjusted associations between MCV-MMA/tHCY, using linear regression. Unadjusted odds ratios (OR) 95% CIs were estimated from logistic regression models. Receiver Operating Curve and the Youden Index were used to identify the MCV level that most accurately distinguished those with abnormal MMA and tHCY (dependent variables) from those without. A positive and significant correlation between MCV-MMA/tHCY was found in the general population between ages 18-85, 0.95 (95% C.I. 0.75-1.17) and 2.61 (95% C.I. 2.15-3.08). In pregnant women, for every unit increase in MCV there was a 19% increase in odds of abnormal MMA, OR 1.19 (95% C.I. 1.08-1.31), p=0.001 and the Area Under the Curve for MCV as a test for abnormal MMA was 78%. An MCV cutoff of 93.1 correctly identified abnormal MMA in pregnant women with 81% sensitivity and 77% specificity. In the general population the MCV test performed poorly in identifying abnormal MMA/tHCY. MCV is an inexpensive measurement that may be useful to screen asymptomatic pregnant women for vitamin B12 abnormalities. This may have a significant impact on reducing adverse neurological outcomes in their children.