Naja annulifera is a dangerous snake that belongs to the Elapidae family. It is found in some of the countries in Sub-Saharan Africa and has caused several accidents in humans and dogs. In this study, we characterized some of the biochemical, toxic and immunogenic properties of N. annulifera venom. We showed that the venom is composed of several proteins, some of which display enzymatic activities, such as phospholipase A2, hyaluronidase, metalloproteinases and serine proteinases. The venom promoted disturbances in the human coagulation system and was cytotoxic to human epidermal cells. Using a mouse model, we showed that the venom promotes local reactions that were reduced with anti-inflammatory drugs. The venom caused systemic inflammation, lung hemorrhage and death. Further, the venom stimulated production of high antibody titers when injected into mice and the antiserum produced was able to inhibit venom-induced death. We therefore conclude that N. annulifera venom contains toxins that play a role in the toxic and inflammatory effects that contribute to the clinical manifestations and death. Moreover, the venom is immunogenic, an important aspect for the production an efficient N. annulifera antivenom.