Many adolescents worldwide (indirectly) grow up with a chronic disease, which may impact their functioning and wellbeing. The objective of this study is to assess whether adolescents with a (family member with a) chronic disease differ from their healthy counterparts in terms of psychosocial functioning. Data from the Dutch 2013 HBSC-survey were used, including 7168 adolescents (Meanage = 13.7, SD = 1.57, 50.5% female). Participants indicated whether they or one of their family members had a long-term (> 3 months) disease or disability (mental/physical) and were categorized into four groups based on disease presence (none, other, self, both). Psychosocial functioning was assessed in terms of life satisfaction, self-rated health, psychosomatic health, mental health problems, support, substance use, physical exercise, screen time, and school liking. Chronically diseased adolescents (n = 162) reported lower life satisfaction, self-rated and psychosomatic health, more mental health problems, lower peer support, more substance use, and less physical exercise compared to healthy peers. Chronically diseased adolescents who also had a family member with a chronic disease (n = 74) showed comparable outcomes on these life domains, although they did not differ from their healthy peers regarding peer support, substance use, and physical activity. Healthy adolescents with a chronically diseased family member (n = 737) reported significantly lower life satisfaction, self-rated and psychosomatic health, more mental health problems, and less family support compared to healthy peers who grew up in healthy families; however, they reported more positive outcomes than adolescents who had a chronic disease themselves. Conclusion: Having a (family member with a) chronic disease is associated with impaired psychosocial functioning on various life domains. Our findings aid in understanding the psychosocial associates of chronic disease and imply that caregivers should be observant of psychosocial problems among vulnerable ...