The correlation between substance use and depression has been emphasized in the literature. Substance use disorders can also adversely affect the caregivers of drug-addicted persons.A cross-sectional study was conducted at the Special Hospital for Addiction Diseases in Belgrade in 2015 to analyze the characteristics, consequences, and health-related quality of life of drug users and their caregivers. The sample comprised 136 users of various substances, and 136 caregivers. A questionnaire on socio-demographic characteristics, the Short Form Health Survey 36 (SF-36), and Beck Depression Inventory were administered to all participants.According to multivariate logistic regression analysis, compared with caregivers, substance users were significantly more frequently male (P < .001), ≤ 39 years old (P < .001), and more frequently reported the use of sedatives (P = .009) and smoking (P < .001). Some level of depression was present in all participants, but severe forms were more frequent in substance users (P = .010). Among substance users, mean scores of SF-36 domains ranged from 56.62-87.17, and among their caregivers, from 50.37-75.07; however, the difference was significant only for the health change domain (P = .037), the score for which was lower in caregivers.Substance users suffered from more severe forms of depression compared to their caregivers, who had lower SF-36 scores in the domain of health change.