Background <p>Sjögren’s disease (SjD) is a chronic autoimmune disease featured by lymphocytic infiltration of exocrine glands and numerous organ involvements, but central nervous system involvement is relatively rare. Due to the variety of symptoms, diagnosis is particularly difficult under certain conditions, which may delay the optimal timing of treatment. Increased clinical awareness and effective pharmacotherapies are urgently needed.</p> Case presentation <p>A case of a 39-year-old female was initially considered to have an intracranial occupancy based upon rapidly progressing nervous symptoms including intermittent fever, parieto-occipital headache, numbness and weakness in the hand, blurred vision, memory impairment and imaging findings, but it was ultimately clarified that she had SjD involving nervous system, with immunological results showing positive antinuclear antibodies (1:640) and anti-SSA/SSB antibodies (+++) in serum and pathological findings suggesting vasculitis of brain. Finally, she was successfully treated with rituximab.</p> Conclusions <p>The onset of SjD may even only manifest as neurological symptoms, which could be easily confused with other systemic or neurological diseases, thus demanding careful differential diagnosis through a detailed medical history and immunological, even pathological examinations to clarify the etiology. Rituximab is an effective treatment option for SjD involving nervous systems, which is an option not commonly featured in standard treatment protocols.</p>