Little is known about the relationship between levels of self-esteem and the development of depression in young adults. The present study investigated the relationship between self-esteem and depression to determine whether self-esteem levels are a risk factor for the development of depression in young adults. This study was conducted with 113 college students aged 19 to 35 (major depressive disorder (MDD) n = 44, Mild Depressive Symptoms (MDS) n = 37, Healthy Control n = 32). The levels of clinical symptoms, self-esteem, resilience, social support, and quality of life, as well as personality traits, were assessed (by Patient Health Questionnaire-9, generalized anxiety disease-7, State-Trait Anxiety Inventory-S, Resilience Appraisal Scale, Rosenberg Self-Esteem Scale, Quality of Life, and NEO-personality inventory (NEO-PI)). The MDS group with high self-esteem reported having the lowest levels of social support, resilience, agreeableness, and extraversion compared to those of the MDD group and control group with high self-esteem. In contrast, the MDS group with low self-esteem showed no differences in social support, resilience, agreeableness and openness according to the NEO-PI scale. Sex and age had no significant impact on the results. Levels of self-esteem are strongly associated with the development of depression. Results suggest that early intervention for depression in young adults needs to focus on improving their levels of social support, resilience, and positive domains of personality. Further studies on the effects of high self-esteem in the development of depression are warranted.