This chapter reviews the current evidence available on excessive daytime sleepiness (EDS), looking for similarities and differences between different metabolic disturbances and for potential confounders such as daytime fatigue and sleep-disordered breathing (SDB). It highlights that EDS can be a feature characterizing infectious or inflammatory diseases, obesity, insulin resistance, renal and hepatic failure, and pulmonary diseases. Daytime sleepiness and sleep disturbances are common complaints in patients with chronic renal failure and end stage kidney disease (ESKD) undergoing dialysis treatment. Few studies have evaluated nocturnal sleep together with daytime sleepiness in patients with pulmonary diseases that lead to severe metabolic alterations such as hypoxia and hypercapnia. The paucity and heterogeneity of the literature on EDS in metabolic conditions intrinsically limits the strength of the association. EDS is frequently associated with chronic metabolic diseases that have high prevalence and heavy socio-economical impact.