In this paper we examine the concept of vulnerability as it relates to the materiality of systems, the exclusion of human physical corporeality, and social exclusion in Luhmann’s theory of social autopoiesis. We ask whether a concept of vulnerability can be included in autopoiesis in order to better conceptualise social exclusion and the excluded, with a view to understanding how, if at all, the dangers posed by this exclusion are mitigated by autopoietic processes. We are emphatically not returning to the human subject over operational systems, but seek instead to develop an understanding of the embodied nature of humans and their vulnerability within an autopoietic framework. We argue that the awareness of the risks to social functional differentiation posed by unmanaged exclusion – disenchantment, disassociation, and, most drastically, dedifferentiation – provided by our analysis indicates why hyper-exclusion must be mitigated.