<h3>Introduction</h3> A previously healthy 12-year-old African American male, who was found to have pancytopenia and electrolyte imbalance in the emergency department (ED), was subsequently diagnosed with systemic lupus erythematosus (SLE) complicated by lupus nephritis. <h3>Case Description</h3> A previously healthy 12-year-old boy presented to the ED with a 3-week history of worsening fatigue, headaches, and dizziness. He also had tactile fever and significant unintentional weight loss compared to one year prior. He had a benign physical examination and vital signs, except for pallor. There was no history of arthralgias, muco-cutaneous lesions, and neuro-psychiatric symptoms. Initial blood work revealed pancytopenia with low reticulocyte count requiring transfusion of platelets and red blood cells. Coombs test was negative, total bilirubin and LDH were normal, ruling out autoimmune hemolytic anemia. There was hyperuricemia, hyperkalemia, hypocalcemia, and hyperphosphatemia, elevated creatinine, proteinuria and hematuria suggesting kidney injury. Initially, a hematologic malignancy with spontaneous tumor lysis syndrome was suspected, and bone marrow biopsy was performed. Bone marrow was hypoplastic, flow cytometry ruled out malignancy. Immunological work-up confirmed the diagnosis of SLE with low C3 and C4 levels, and highly positive ANA, anti-dsDNA, anti-Smith, anti-SS-A, anti-SS-B. Anti-phospholipid antibodies were negative. The patient responded favorably to high-dose methylprednisolone followed by maintenance treatment with oral prednisone and mycophenolate mofetil. <h3>Discussion</h3> Aplastic anemia is a rare initial presentation of pediatric SLE, its exact pathogenic mechanism remains unknown. The diagnosis of SLE should be suspected in cases of aplastic anemia with no alternative explanation. Early diagnosis and treatment can prevent life-threatening complications.