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The management of the bubonic plague in colonial Lagos, Nigeria, unavoidably put the indigenous population at the receiving end of massive social disruptions. The impact of the control measures on the social and political temperament of the area with the reactions it elicited among the indigenous people is absent from the historiography of the bubonic plague in Lagos. This study draws upon primary sources (first-hand accounts and interviews) to provide insight into how residents in colonial Lagos grappled with the plague and the colonial state’s attempts to control the epidemic and govern the city. The central argument of this paper is that at a time of growing nationalism among an increasingly politically conscious African educated class, public health measures adopted to control the bubonic plague only served to breed political unrest and intra-party antagonism that threatened the social thread of the city. Lagos political space provides us with the opportunity to study how medical issues became entangled with nationalist agitation. Evidence for the study was drawn from archival materials sourced from the National Archives of Nigeria, Ibadan; the British National Archive, London; and oral interviews conducted in Lagos.