Objective We report on a patient who presented with complete ophthalmoplegia as a first symptom of fatal invasive aspergillosis. Case report We present the clinical course of an immunocompromised 68-year-old man with unclear painless loss of vision, ptosis and ophthalmoplegia of the right eye lasting for 10 days which was referred from an ophthalmological outpatient clinic. He had a history of kidney transplantation after renal failure, diabetes mellitus II, and coronary heart disease. He was on immunsuppressive therapy with tacrolimus, mycophenolate and prednisolone since renal transplantation. The initial cranial magnetic resonance imaging (MRI) was unremarkable. The additional thin section computed tomography (CT) of the paranasal sinuses was suspicious for bone erosion of the superior wall of the right sphenoidal sinus. Initial laboratory testing and cerebrospinal fluid were without pathological findings. When the patient showed signs of generalised sepsis he was transferred to the intensive care unit. Due to fulminant sepsis it was not possible to perform the planned biopsy. The patient died a few days later of cardio-respiratory insufficiency. The consecutive autopsy revealed invasive aspergillosis of paranasal sinuses with infiltration into the orbita and intracranial spreading into sinus cavernosus. Autopsy also showed aspergillus pneumonia. Discussion Invasive aspergillosis of the paranasal sinuses and the skull base is most often a lethal condition in immunocompromised patients. Therefore, rapid diagnostics applying radiological (CT and MRI) and surgical procedures (biopsy) and immediate ignition of antimycotic treatment can be life-saving.