Objective: Problematic video-gaming or social media use may seriously affect adolescents’ health status. However, it is not very well known which health-related problems are most strongly related to these issues. To inform the development of prevention and intervention strategies, this study aims to gain a better understanding of the health-related problems and demographical factors associated with problematic video-gaming or social media use in early adolescence. Method: A cross-sectional analysis was performed on data collected by two Municipal Health Services in the Netherlands in 2013-2014. In this survey among youth, 21,053 students from secondary schools (mean age 14.4 years) completed a web-based questionnaire. Multivariate analyses were carried out to assess the strength of the associations between mental health problems, life-events, lifestyle and substance use as independent variables, and problematic video-gaming and problematic social media use as dependent variables. Results: Of the participating students, 5.7% reported problematic video-gaming and 9.1% problematic social media use. Problematic video-gaming was most strongly associated with conduct problems, suicidal thoughts (all medium effect sizes, OR >= 2, p < 0.01), sedentary behavior (large effect size, OR >= 3, p < 0.01), and male gender (large effect size). Problematic social media use was highly associated with conduct problems, hyperactivity and sedentary behavior (all medium effect sizes). Additionally, female gender and non-Western ethnicity were relevant demographics (large and medium effect size). Conclusions: Most mental health problems were consistently associated with both problematic video-gaming and problematic social media use, though associations were only practically relevant for conduct problems (both groups), suicidal thoughts (problematic video-gaming) and hyperactivity (problematic social media use). This study also highlights sedentary behavior as health risk as it was associated with both problematic video-gaming and problematic social media use. Interventions for young problematic video-gamers or social media users should take into account mental health and physical activity.