Steroid-dependent nephrotic syndrome (SDNS) is a common type of childhood nephrotic syndrome. Remission following steroid therapy is achieved in 80-90% of the patients, while the remainder show steroid-resistant nephrotic syndrome (SRNS). Rituximab is an anti-CD20 chimeric monoclonal antibody with proven therapeutic effects in several diseases and has been used with great success in the treatment of NS since its discovery. We report a case of a 4-year-old girl diagnosed with SDNS at the age of 3. As treatment with steroids, enalapril, and mycophenolate failed to produce complete remission, rituximab was initiated, and remission was successfully achieved after administration of the first dose. Due to this response, rituximab therapy was continued; however, a day after being admitted to the nephrology ward for the second dose, she started to develop a high fever, which reached up to 40°C. In addition, she also displayed symptoms of upper respiratory tract infection and an ulcerated wound on her left cheek. The patient became drowsy with reactive pupils, cold peripheries, and weak peripheral pulses. The capillary refill time was prolonged to 3-4 seconds and it was decided to withhold the second dose of rituximab. The patient was shifted to the PICU as a case of septic shock secondary to facial cellulitis and started on inotropes (epinephrine and norepinephrine), meropenem, vancomycin, and hydrocortisone 15 mg. Thereafter, surgical debridement of the wound was carried out. The patient remained in remission with regard to nephrotic syndrome and was discharged in a healthy condition. In conclusion, rituximab used in conjunction with steroids and other immunosuppressants may increase the risk of serious infections like necrotizing fasciitis (NF). Further studies are needed to explore the relationship between rituximab and NF.