Rationale: Nitrous oxide (NO) is a commonly used drug in medical practice, restoration, and the automobile industry. Recreational abuse is an emerging public health problem owing to its accessibility and drug properties.

Patient concerns: A 25-year-old male was hospitalized with acute psychosis and lower-extremity sensorimotor proprioceptive ataxia due to nitrous oxide abuse.

Diagnosis: Laboratory studies confirmed a vitamin B12 deficiency. Magnetic resonance imaging of the spinal cord showed normal findings. Electrophysiological testing confirmed length-dependent sensorimotor polyneuropathy, with a predominant motor component and axonal degeneration.

Intervention and outcomes: Abstinence from toxic substances was suggested, and vitamin B12 substitution was introduced. The patient was lost to follow up.

Lessons: Nitrous oxide toxicity is multisystemic and is thought to result from vitamin B12 inactivation. Recent case reports postulated direct paranodal lesions resulting from nitrous oxide consumption. Neurological, neuropsychiatric, and hematological toxicities are among those explored in this case report. Correction of the functional vitamin B12 status and nitrous oxide abstinence are essential in the treatment process.