ABSTRACT ‘Locked-in syndrome (LIS)’ is a neurological disorder, often missed initially and can have grave consequences. A rare case of LIS caused due to folic acid deficiency-induced hyperhomocysteinemia is being described here. A 16-year-old boy presented with complaints of sudden onset weakness of all the four limbs with loss of voice for one day. All the tendon reflexes were increased, bilateral planters were extensor and sensory system was intact. Patient was conscious and responded to verbal commands by ocular movements in vertical direction. Hence, a diagnosis of LIS was made. Magnetic resonance imaging of the head revealed an acute infarct in ventral pons. Serum homocysteine level was elevated (20.65 μmol/l) and folic acid level was severely low (1.7 nmol/ml). Cause of LIS was found to be hyperhomocysteinemia induced stroke in the pons, related to folic acid deficiency. The patient was managed with antiplatelet agents and folic acid supplementation and was discharged subsequently. Recognition of LIS is important as casual remarks at bedside can severely traumatize an already paralyzed but conscious and awake patient. Folic acid deficiency can lead to hyperhomocysteinemia, which can cause strokes and even LIS. Prevention of hyperhomocysteinemia may possibly prevent such neurological disasters.