Cefixime and Ofloxacin is one of the common antibiotic combination used in India. Though antibiotic combination therapy can possess with higher complications but useful in various conditions. Cefixime and Ofloxacin induced Steven Johnson Syndrome is common in patients and can be easily identified but situations turns opposite when same complication developed in a patient with Systemic Lupus Erythematosus because, the complication in both the conditions mimic each other therefore, careful examination with supported various laboratory data and past medical/medication history helps proper identification of such conditions. Management of Steven Johnson Syndrome requires prompt withdrawal of suspected/offended drug along with supportive therapy which includes; fluid & electrolyte replacement, systemic and topical corticosteroids, topical anesthetics and antiseptic mouth washes.