Introduction: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency, in which infections are the main presenting symptoms. Moreover, patients may also experience inflammatory and autoimmune manifestations. With proper management of infections, patients now survive to adulthood, and inflammatory manifestations have become more prominent problems. Treatment of the inflammatory manifestations in CGD is challenging and requires a multidisciplinary approach. Since tumor necrosis factor (TNF)-alpha has been cited as having a possible role on inflammatory conditions in CGD, etanercept, an anti-TNF agent, may represent a major advance in the management of inflammatory manifestations. Case Presentation: In this report, we described a 15-year-old boy, suffering concurrently both from human leukocyte antigen (HLA)-B27-positive chronic arthritis and CGD, whose arthritis did not respond to treatment with methotrexate and ibuprofen. Remission was achieved 6 months after etanercept initiation and during the next 18 months on medication, we did not encounter any signs of severe infections. Conclusion: Treatment of inflammatory conditions in CGD patients is still challenging in view of the lack of evidence-based therapeutic options. In this study, we report the first pediatric CGD case, in which chronic arthritis was successfully treated with etanercept.