The concept of human security is increasingly accepted as being integral to contemporary notions of national security because of a growing awareness of the importance of individual and societal well-being to national, regional and global peace and stability. Health is thus considered an important component of the predominant vision of human security. However, the precise meaning and scope of global health security remains contested partly due to suspicions about clandestine motives underlying framing health as a security issue. Consequently, low and middle-income countries have not engaged global discourse on health security. This has resulted in an unbalanced global health security agenda shaped primarily by the interests of high-income countries. It narrowly focuses on a few infectious diseases, bioterrorism and marginalizes health security threats of greater relevance to low and middle-income countries. Focusing primarily on countries in the WHO-AFRO region (the African Group), this paper examines the implications of the participation deficit by the African Group of countries on their shared responsibility towards global health security. The potential benefits of regional health security cooperation are analyzed using selected critical health security threats in the Southern African Development Community (SADC). This paper concludes that the neglect of the African Group health security interests on the global health security agenda is partly due to their disengagement. Ensuring that multilateral health security cooperation includes the African Group’s interests require that they participate in shaping the global health security agenda, as proposed in a putative SADC health security cooperation framework.