Abstract Background Certain factors, such as depressive symptoms and binge drinking, may be linked to young adults’ ability to attain an acceptable level of functioning on specific life-domains (i.e. self-sufficiency). We studied the association of contextual factors and health indicators with self-sufficiency in young adults. Methods We used both baseline (n = 755) and 6-months follow-up (n = 200) self-reported questionnaire data of intermediate vocational education students (16–26 years). The questionnaire included the adapted Dutch self-sufficiency matrix (SSM-D), which addresses self-sufficiency regarding 11 life-domains (e.g. finances and housing). The questionnaire also included potentially associated contextual factors (e.g. socio-demographic characteristics) and health indicators (e.g. sickness absence from school). Ordinal (overall self-sufficiency: self-sufficient on 11, 10, 9 or ≤ 8 life-domains), and logistic (self-sufficiency per life-domain: self-sufficient yes/no) regression models were applied. Results The studied population was 18.6 years on average (SD 2.04), and 73.6% were female. Cannabis use was associated with a lower overall self-sufficiency category at baseline (OR = 0.57, 95% CI = 0.33–0.99), as were an increase in sick days (OR = 0.94, 95% CI = 0.91–0.98) and an increase on the scale of depressive symptoms (OR = 0.87, 95% CI = 0.85–0.89). An increase in sick days and an increase on the scale of depressive symptoms were associated with lower odds of being self-sufficient on three and ten life-domains, respectively (p < 0.05). An increase on the scale of depressive symptoms was associated with a lower overall self-sufficiency category 6-months post-baseline (OR = 0.90, 95% CI = 0.86–0.93). Conclusions Our findings underline the importance of addressing self-sufficiency, sickness absence, and depressive symptoms, preferably before the transition from adolescence to young adulthood has begun.