This qualitative research study explored the psycho-educational and social factors that contribute to anxiety in orphaned adolescent students in a secondary school in Welkom, Free State, South Africa. A multiple case-study design was used to collect data from eight adolescents (4 males and 4 females) aged between 11 and 14 years. The participants were purposefully selected from a mainstream secondary school in a suburban area in Welkom. Data collection through individual and semi-structured interviews was supplemented with collages and a focus group discussion with the participants. The psychological findings indicated that the orphaned adolescents experienced anxiety concerning their own death as well as that of their significant others. From an educational perspective, their anxiety was due to the negative attitudes of their teachers. Furthermore, the social factors that contributed to their anxiety included economic survival, grieving according to cultural beliefs, and the isolation they experienced. Adopting a social ontogenetic theoretical perspective, the authors provide guidelines for educational psychologists on what psycho-educational and social support interventions could be provided for orphaned adolescents.