Objective: To determine the impact of antiepileptic drugs and nutrition therapy on the plasma carnitine concentration in patients with severe motor and intellectual disabilities.Subjects & Methods: Plasma carnitine concentration was measured in 129 outpatients and inpatients with severe motor and intellectual disabilities to examine its association with feeding method and administration of sodium valproate (VPA) and phenobarbital (PB).Results: Among patients on oral feeding, the concentration of free carnitine was significantly lower in the VPA(+) PB(+) group (29.5 μmol/L) compared with the VPA(-) PB(-) group (48.0 μmol/L). Among patients on tube feeding, the concentration of free carnitine was significantly reduced to 30.5 μmol/L even in the VPA(-) PB(-) group, and the reduction was more prominent with the administration of VPA and PB.Conclusion: We demonstrated that the administration of VPA and PB reduced the plasma carnitine concentration in patients with severe motor and intellectual disabilities, and the use of a carnitine-free enteral formula enhanced this reduction synergistically. Our findings suggest that these antiepileptic drugs and nutrition therapy using carnitine-free enteral formula may increase the risk of carnitine deficiency.