Stevens-Johnson syndrome (SJS) is a severe and rare immune-mediated cutaneous reaction usually induced by drugs or infections. Few case reports have demonstrated SJS associated with adult systemic lupus erythematosus (SLE), and rarely in juvenile SLE (JSLE) patients. However, to the best of our knowledge the prevalence of this life-threatening cutaneous disease in the pediatric lupus population has not been studied. Therefore, from January 1983 to December 2010, 5508 patients were followed-up at the Pediatric Rheumatology Unit of our University Hospital and 279 (5%) of them met the American College of Rheumatology (ACR) classification criteria for SLE. Only one (0.4%) of our JSLE patients had SJS and was described. This female patient was diagnosed with JSLE at 14 years old. After four years of follow-up, she was hospitalized due to congestive heart failure and renal insufficiency. During hospitalization, the patient developed sepsis with positive blood culture for Stenotrophomonas maltophilia and was treated with vancomycin and meropenem. One week later, she developed septic shock and chest x-ray showed acute widespread pulmonary infiltrate. Antimicrobials were changed to linezolid and trimethoprim-sulfamethoxazole. After four days, the blood culture isolated Staphylococcus aureus resistant to vancomycin, and she presented with erythematous cutaneous lesions involving her face, trunk, and limbs, with evolution in a few hours to diffuse hemorrhagic vesicles and blisters. Epidermal detachment was observed on 5% of the body surface area. Concomitantly, she had conjunctivitis, cheilitis, oral erosions, and hemorrhagic crust on the nasal mucosa. Vulva, vagina, and perianal erosions were also evidenced. The diagnosis of SJS was established and intravenous immunoglobulin was promptly administered. Three days later, she died of pulmonary hemorrhage. The autopsy findings demonstrated generalized infection and widespread subepidermal detachment with necrotic keratinocytes. In conclusion, SJS is a rare and severe vesiculobullous disease in a pediatric lupus population and is probably associated with infections and drug therapy.