Purpose.To describe a corneal co-infection with the fungusScedosporium apiospermumandAcanthamoebathat result in spontaneous corneal perforation.Methods.A 27-year-old man presented due to severe ocular pain in his left eye caused by a corneal ulcer. The patient was injured 7 days before presentation by metallic thread contaminated by sewage. Corneal scrapping and deep stromal biopsy were obtained and stained for microscopic evaluation with periodic acid-Schiff, Giemsa, and Gomori's methenamine silver stains. Samples were sent for aerobic and anaerobic bacterial and fungal cultures.Results.Corneal biopsy and corneal scrapping showed viableAcanthamoebacysts in the corneal stroma andS. apiospermummicelle, respectively. The fungal culture was sensitive to ketoconazole, miconazole, econasole, and traconazole. Devastating corneal perforation occurred despite aggressive antifungal and antiamoebic topical and systemic treatment initiated after diagnosis. The corneal button showed a necrotic tissue devoid of inflammatory cells and microorganisms.Conclusion.S. apiospermumandAcanthamoebamay co-infect immune privilege sites, such as the cornea, in immunocompetent hosts. Compromised corneal surface, e.g., after trauma by sewage-contaminated objects, may increase the susceptibility for such devastating co-infection. Prevention may be possible by use of protective eyewear by high-risk individuals. Treatment should be initiated promptly with broad-spectrum antimicrobial agents after ocular injury by sewage-contaminated objects. Repeated corneal cultures and biopsies, if the cultures are negative, are warranted. Corticosteroids should be withheld until the causative agents are identified and targeted treatment is initiated.