Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects multiple organ systems, significantly impacting the cardiovascular system. One potential complication of acute SLE flare is the development of pericardial effusion which can lead to potentially life-threatening consequences if not promptly identified. In this report, we describe the case of a 35-year-old female with a known history of SLE who developed rapid-onset, large-volume pericardial effusion with tamponade during a lupus flare. She received emergency treatment involving pericardiocentesis and was administered high doses of glucocorticoid and immunosuppressive medication. As a result, the pericardial effusion gradually resolved, and the patient’s symptoms improved. This case emphasizes the significance of immediately identifying and managing swiftly progressing pericardial effusion in SLE patients. This is crucial as it can lead to severe and potentially lethal complications.