The current study examined the relationship between plasma orexin-A and sleep in obesity. Concentrations of orexin-A and sleep were evaluated in 26 obese, 40 morbid obese and 32 healthy-weight participants. The sleep monitor Actiwatch AW7 and the Pittsburgh Sleep Quality Index were used to evaluate sleep. The Symptom Checklist-90-Revised was administered to assess symptoms of psychopathology. A higher weight status was associated with elevated orexin-A levels (p = .050), greater depression, anxiety and somatization symptoms (all: p < .001), and impoverished self-reported sleep quality (p < .001). A quadratic trend was found in objective sleep time, being longest in the obese group (p = .031). Structural equation modelling showed plasma orexin-A to be related to poor total sleep quality, which in turn was associated with elevated body mass index. Our data confirm an interaction between elevated plasma orexin-A concentrations and poor sleep that contributes to fluctuations in body mass index.