Depression (DEP) is one of the main disabling diseases and is considered a contributor factor for erectile dysfunction (ED). Both of these conditions may be associated with hormonal changes and sleep disturbances. We aimed to evaluate the interaction between ED complaints and depression symptoms on sleep parameters, hormone levels and quality of life in men. This was a cross-sectional study of 468 men aged 20–80 years. The participants were classified according to the presence of ED and/or DEP in groups of healthy individuals, ED, DEP and DEP with ED (DEP-ED). All participants completed questionnaires about sleep, clinical history and quality of life, and underwent polysomnography with blood collection the following morning. ED participants showed higher frequency of insomnia symptoms (65.5%), whereas DEP group had more complaints of difficulty in falling asleep and early morning awakening. In the polysomnography, all groups showed similar parameters. No differences were found in cortisol and total testosterone levels; however, free testosterone levels and the physiological domain of quality of life were lower in DEP-ED group. ED and DEP, as independent factors, negatively affected subjective sleep parameters. The interaction between these factors led to a low quality of life and was related to a decrease in free testosterone levels.