Introduction <p>Systemic lupus erythematosus (SLE) is a complex autoimmune disease with diverse clinical manifestations, including thrombotic complications. While venous thromboembolism is well-recognized in SLE, central venous sinus thrombosis (CVST) as an initial presentation is exceedingly rare. The prothrombotic state in SLE is often linked to antiphospholipid antibodies; however, alternative mechanisms, such as complement activation and immune-mediated endothelial dysfunction, may also contribute to thrombosis. Early recognition and intervention are crucial to preventing severe neurological complications.</p> Case Presentation <p>We report a case of a 26-year-old female who presented with a two-day history of persistent headache, nausea, and vomiting. Neuroimaging revealed CVST, and further serological workup confirmed SLE, with positive antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), and low complement levels, though antiphospholipid antibodies were absent. The patient was initiated on anticoagulation with acenocoumarol despite the presence of intracranial hemorrhage, along with immunosuppressive therapy using pulse corticosteroids and cyclophosphamide. This approach effectively controlled disease activity, prevented thrombotic progression, and led to clinical and radiological improvement along with normalization of laboratory parameters.</p> Conclusions <p>This case underscores the importance of recognizing SLE as a potential underlying cause in atypical thrombotic events and highlights the critical role of early anticoagulation and immunosuppression in managing SLE-associated CVST. Further research is necessary to explore the pathogenesis and refine management strategies for thrombotic events in SLE.</p>