Tumor necrosis factor (TNF)-alpha is a pro-inflammatory cytokine that plays an important role in the pathogenesis of a variety of autoimmune diseases. TNF-alpha inhibitors have been shown to offer clinical benefits in the treatment of autoimmune and inflammatory disorders, including rheumatoid arthritis, ankylosing spondylitis (AS), and Crohn's disease. Occasionally, these agents have been associated with infectious complications because of their immunosuppressive activity. Globally, several cases of infections associated with TNF-alpha inhibitors have been reported. However, Aspergillus infection associated with etanercept is very rare. We report a case of chronic necrotizing pulmonary aspergillosis in a 51-year-old man with AS that developed after treatment with etanercept.