This study investigated the longitudinal relation between general well-being and self-esteem of male adolescents with severe psychiatric disorders. Moreover, the transition out of secure residential care was studied. Adolescents (N = 172) were assessed three times with 6 months between each assessment. The sample comprised adolescents who were admitted throughout the entire study (n = 116) and who had been discharged at 6/12 months follow-up (n = 56). General well-being and self-esteem were stable concepts over time. The relation between general well-being and self-esteem differed for both groups. Among the admitted group general well-being positively predicted self-esteem and self-esteem negatively predicted general well-being from Time 2 to Time 3. Among the discharged adolescents, self-esteem at Time 1 positively predicted general well-being at Time 2 and general well-being at Time 2 positively predicted self-esteem at Time 3. Changing social contexts, as well as problems experienced during the transition out of secure care, might affect this relationship.