Sepsis, cellulitis, and necrotizing fasciitis rarely have been described as causes of compartment syndrome. We report a case in which forearm compartment syndrome presented as the initial symptom of systemic infection. Vibrio vulnificus, the etiologic pathogen of the compartment syndrome, was isolated from wound and blood cultures. The patient was treated with systemic antibiotic treatment and multiple forearm fasciotomies. The infectious process progressed rapidly, however and due to underlying liver insufficiency, the patient died of hepatorenal syndrome. This case illustrates the nature of V vulnificus infections, which are characterized by shellfish transmission, predilection for soft tissue seeding, and a fulminant course in the compromised host.