A 55-year-old woman developed severe unilateral headaches, periocular numbness, and Horner syndrome after presenting with symptoms consistent with Lyme disease. The combination of Horner syndrome and periocular headache and numbness constituted a diagnosis of Raeder paratrigeminal neuralgia. Although the headaches resolved with antibiotic treatment, the Horner syndrome persisted for at least 1 year. This case expands the spectrum of neurologic manifestations of Lyme disease to include postganglionic Horner syndrome as well as Raeder paratrigeminal neuralgia.