Pyridoxine (vitamin B6) toxicity is a well-known cause of primary sensory, length-dependent, axonal polyneuropathy. Although sensory symptoms predominate, autonomic symptoms have also been reported in some cases. To date, there is no objective evidence of autonomic dysfunction reported in the literature. We present the case of a 41-year-old woman with 2 years of progressive burning pain, numbness, tingling, and weakness in a stocking-glove distribution who was found to have severe pyridoxine toxicity. Concurrent presence of large and small fiber nerve dysfunction was noted in the form of abnormal electromyography/nerve conduction study demonstrating a chronic sensory polyneuropathy and autonomic testing demonstrating abnormal responses to quantitative sweat testing and cardiovagal function testing. This case highlights the need for consideration of small fiber nerve damage by obtaining autonomic testing in cases of pyridoxine toxicity.