A fatal case of Physalia physalis (Portuguese man-o'-war) envenomation occurred on the Florida Atlantic coast in 1987. Despite appropriate beachside first aid, the patient was conscious only several minutes before having primary respiratory arrest and, later, cardiovascular collapse that resulted in death. Discharged nematocysts were still visible on the injured stratum corneum five days after envenomation. Additional treatment maneuvers suggested by this case include testing the tentacle fragments found on the victim's skin before their removal to ensure that nematocyst firing has been counteracted. We document the first human fatality caused by P physalis envenomation.