Background <p>Sleep plays a crucial role in physical and mental health, and its lack is associated with chronic non-communicable diseases (CNCDs). To investigate how anxiety and depression influence this relationship, especially during the pandemic, is essential.</p> Objectives <p>To evaluate the association of CNCDs with sleep quality, and mediation by anxiety and depression symptoms during the COVID-19 pandemic.</p> Design&#xa0;and setting <p>Population-based cross-sectional serological survey of 1,511 adults in the Iron Quadrangle region, Brazil.</p> Methods <p>The exposure variable was CNCDs. The outcome variable was sleep quality evaluated through the Pittsburgh Sleep Quality Index (PSQI). Anxiety and depression symptoms were assessed using General Anxiety Disorder 7 (GAD-7) and Patient Health Questionnaire 9 (PHQ-9), respectively. For testing the mediator factors, the path analysis was conducted.</p> Results <p>Poor sleep quality was found in 52.5% of the population; 23.4% had symptoms of anxiety, and 15.0% of depression. Furthermore, 39.8% reported at least one CNCD, with a maximum of five. In multivariate analysis, we found for each unit increase in the number of CNCDs, the chance of poor sleep quality increases by 39% (OR: 1.39; CI_95%: 1.09–1.76). In mediation analysis, the presence of anxiety and depression symptoms explained 6.5% and 36.1% of the association between CNCDs and poor sleep quality, respectively.</p> Conclusions <p>Individuals with CNCDs had poor sleep quality during the COVID-19 pandemic. Furthermore, symptoms of anxiety and depression explained part of the association. Therefore, our study highlights the importance of evaluating the sleep quality and mental health of individuals with CNCDs during pandemics.</p> Graphical Abstract <p></p>