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In animals, group living comes at the cost of increased pathogen exposure. In kin groups, social immune behaviours offset that cost and reach their most complex expression in eusocial insect societies. In the nests of these societies, collective social behaviours can modify the patterns of individual interactions across space, reducing the ability of pathogens to reach the reproductive core of the colony (organizational immunity). To be effective, these behaviours must separate infected and uninfected individuals; implying that the efficacy of social immune behaviours may depend upon nest structure. The role of nest space has received little attention, and most knowledge of social immune behaviour in social insects is based on the study of generalist entomopathogenic fungi. We examine the social immune behaviours involved in the interaction between the supercolonial, invasive tawny crazy ant (Nylanderia fulva) and its specialist, intracellular, microsporidian pathogen Myrmecomorba nylanderiae, to ask how nest structure influences social immunity. By manipulating nest structure, we demonstrate that preventing pathogen transmission to the colony core requires a multi-chambered nest. Without which, social immune function was lost, and disease transmission was universal. To understand how nest space enhances social immune efficacy, we first confirm that workers within tawny crazy ant nests form spatially and behaviourally segregated social sub-networks. We then find that infected ants introduced into the colony core migrate to the colony periphery, while uninfected ants do not. Behavioural tests indicate that, despite the infection being internal, uninfected ants can detect the infection status of a worker; thus, behaviours enforcing spatial segregation could be triggered by either party. Additionally, infected ants alter the behavioural tasks they perform, assuming more corpse removal tasks, particularly infected corpse removal, and reducing their efforts in foraging and brood care. With some exceptions, the social immune behaviours expressed by this supercolonial ant in response to microsporidian infection correspond to immune defence behaviours employed to defend against generalist entomopathogenic fungi. These behaviours appear to be conserved, generalized responses to pathogen infection among social insects.