From the eighteenth century patients might use ‘uneasiness’ / inquiétude to describe both a physical sensation and a personal anxiety. This double definition reflects the deep interrelation between emotion and sensation in the period. Inquiétude was embedded in a specific historical context, defined by humoral medical discourse, by the practice of self-writing, by the doctor-patient relationship, and by a semantic confusion in the use of certain words. Analysis of the different uses of inquiétude in nineteenth- and twentieth-century French novels shows that it increasingly described a mental state, such as an anxiety, but that the sensorial meaning persisted discreetly in different ways. Elements of neurophysiological theories and relevance theory offer some tools to bridge the gap between the two narrative genres and historical contexts.