Background Impulsivity and substance use disorders (SUD) can be related to the same environmental factors. In this study, we intended to evaluate the dopaminergic function in imprisoned SUD offenders through the determination of s-COMT activity. Methods The study included 46 male individuals from a Portuguese penal institution. The participants were assessed through a battery of standardised instruments: Psychopathy Checklist-Revised (PCL-R), Barratt Impulsivity Scale Version 11 (BIS-11), and the European version of the Addiction Severity Index (EuropASI). s-COMT erythrocyte activity was evaluated. Results Overall, 73.9% (n=34) of the individuals had Antisocial Personality Disorder (ASPD) and 58.7% (n=27) presented SUDs. We evidenced, for the first time, that, in SUD individuals, s-COMT activity is correlated with the severity of drug dependence (EuropASI) (p<0.05), and with BIS-11 factors self-control (p<0.0001) and non-planning (p=0.002). Conclusions This study opens new perspectives regarding the pharmacological intervention on drug dependence through the interference on dopamine pathways.