Tehran University of Medical Sciences Case Reports in Clinical Practice 2538-2683 7 6 2023 03 12 313 318 Mohsen Koosha Neurosurgery Department, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Golfam Mehrparvar Neurosurgery Department, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Sepideh Paybast Multiple Sclerosis Research Center, Neuroscience Institute; Tehran University of Medical Sciences, Tehran, Iran. 2022 08 12 2022 11 05 Rituximab is a CD20 depleting agent, widely used as an off-label disease- modifying treatment (DMT) in treating multiple sclerosis (MS). The present study aimed to report the first case of rhino-sino-cerebral mucormycosis in a patient with secondary progressive MS (SPMS), treated with rituximab.The patient was a 38-year-old man with a history of SPMS treated with rituximab, who developed subacute left vision loss and impaired ocular movement. He also mentioned a concomitant severe headache and cheek swelling. Based on the brain and orbital magnetic resonance imaging (MRI) findings, rhino-sino-cerebral mucormycosis was suspected. Subsequent endoscopic examination confirmed the diagnosis. He underwent medical treatment with amphotericin B liposomal and surgical debridement leading to a significant clinical recovery. He was eventually discharged home with a solid recommendation to discontinue rituximab. The present report indicates a case of SPMS treated with rituximab, who developed rhino-sino-cerebral mucormycosis. https://crcp.tums.ac.ir/index.php/crcp/article/view/728