Lyme neuroborreliosis is diagnostically challenging because of its diverse manifestations. Literatures studies have documented a neurological spectrum that includes radiculoneuritis, lymphocytic meningitis, and cranial neuropathy in the early disseminated stage of Lyme’s disease. Severe and refractory hyponatremia is a rare association with Lyme neuroborreliosis, further misleading clinicians to misdiagnose the syndrome of inappropriate antidiuretic hormone secretion (SIADH). This case report describes a 58-year-old woman who developed progressive lower extremity weakness and paresthesia, cerebellar ataxia, and persistent hyponatremia. The patient was hospitalized to rule out cerebral vascular stroke, Guillain-Barre, and SIADH. Lyme neuroborreliosis was diagnosed and treated with 2mg ceftriaxone from clinical suspicion. With treatment initiation, the patient’s neurological symptoms of gait instability, hyponatremia, and bilateral lower extremities weakness gradually resolved.