Treatment of locally advanced or metastatic squamous cell carcinoma is difficult and treatment options are limited. Cemiplimab is a monoclonal antibody against the programmed death-1 receptor (PD-1), which is approved in the USA for the treatment of locally advanced or metastatic squamous cell carcinoma. This case report describes a 74-year-old patient who was treated with cemiplimab for advanced cutaneous squamous cell carcinoma. Treatment with cemiplimab resulted in a complete remission. Following the first infusion with cemiplimab, the patient was admitted to hospital due to fever of unknown origin, epileptic seizures and neurological deficits. An immune-mediated meningoencephalitis was diagnosed. The neurological deficits completely resolved under systemic high-dose corticosteroid treatment. Therapy with PD-1 antibodies can achieve durable responses in advanced or metastatic squamous cell carcinoma. Therapy with immune checkpoint inhibitors can lead to severe immune-related adverse events. Timely interdisciplinary management with early diagnosis and initiation of therapy are essential to prevent permanent damage.