The present study was aimed at investigating the psychosocial challenges and coping mechanisms of female prison inmates. The study was conducted in Addis Ababa, Kaliti federal prison. Two hundred twenty female participants were selected using cluster sampling. A self-reported questionnaire that consisted of questions on social background, levels of depression, anxiety, and stress, frequency of loneliness, types of coping mechanisms, available of support and care services was employed. Four prison staffs were selected by judgmental sampling method and interview was conducted. The data obtained from prison inmates were analyzed using SPSS version 21. The findings indicate that depression was positively and strongly correlated with anxiety (r=.62, p