Venomic analysis of the venoms of Naja nigricollis, N. katiensis, N. nubiae, N. mossambica and N. pallida revealed similar compositional trend. The high content of cytotoxins and PLA2s may account for the extensive tissue necrosis characteristic of the envenomings by these species. The high abundance of a type I ±-neurotoxin in N. nubiae may be responsible for the high lethal toxicity of this venom (in rodents). The ability of EchiTAb-Plus-ICP® antivenom to immunodeplete and neutralize the venoms of African spitting cobras was assessed by antivenomics and neutralization tests. It partially immunodepleted 3FTx and PLA2s, and completely immunodepleted SVMPs and CRISPs in all venoms. The antivenom neutralized the dermonecrotic and PLA2 activities of all African Naja venoms, whereas lethality was eliminated in the venoms of N. nigricollis, N. mossambica and N. pallida, but not in those of N. nubiae and N. katiensis. The lack of neutralization of lethality of N. nubiae venom may be of medical relevance only in relatively populous areas of the Saharan region. The impaired activity of EchiTAb-Plus-ICP® against N. katiensis may not represent a major concern. This species is sympatric with N. nigricollis in many regions of Africa, although very few bites have been attributed to it.