Background: Well-being encompasses physical, mental, social, and cultural aspects. Sleep quality and pathologies are among the objective conditions jeopardising it. Chronic insomnia, inflammatory-based diseases, and mood disorders often occur in a single cluster, and inflammation can negatively impact sleep, potentially harming well-being. Some evidence from specific clinical populations suggests that also some resolved past diseases could still have an impact on present sleep quality and well-being. The aim of the present study is to investigate, in the general population, whether and to what degree well-being and insomnia are associated with resolved pathologies. Methods: A cross-sectional survey (IPSAD®) was carried out using anonymous postal questionnaires that investigated past and present general health, well-being, and insomnia. A total of 10,467 subjects answered the questionnaire. Results: Several classes of both current and resolved pathologies resulted in increased odds ratios for current insomnia (odds ratios = 1.90; 1.43, respectively) and impaired well-being (odds ratios = 1.75; 1.33, respectively), proportional to the number of the displayed pathologies. Notably, both current and resolved past psychiatric disorders were strongly associated with both current impaired well-being (odds ratios = 5.38; 1.70, respectively) and insomnia (odds ratios = 4.99; 2.15, respectively). Conclusions: To explain these associations, we suggest that systemic inflammation conveyed by several medical conditions disrupts homeostatic processes, with final effects on sleep quality and behaviour.