This study attempts to identify a mediation effect of self-esteem in relation to stress and comprehensive well-being of upper-level elementary school children. To this end, the researchers conducted a survey on 450 fifth grade students in four elementary schools in Gyeonggi province, South Korea. The researchers asked questions to measure the levels of stress, self-esteem, and comprehensive well-being. The analysis of survey data was based on reliability tests of each measure, correlation coefficient analysis of major variables, multiple regression analysis, and verification of mediation effects. According to the results of multiple regression analysis, which we conducted to see what impact sub-factors of stress have on comprehensive well-being, stress related to parents, friends, teachers, and school had a negative effect on the respondents' comprehensive well-being. In particular, friend-related stress had the highest degree of impact on the respondents' well-being. The results of verification of mediation effect of self-esteem in the relationship between stress and comprehensive well-being demonstrate that self-esteem, on the whole, and self-esteem for each sub-factor (general self-esteem, social self-esteem, self-esteem at home, and self-esteem at school) had a partial mediation effect which was statistically significant. That is, stress can have a negative effect on comprehensive well-being directly, while reducing the level of comprehensive well-being indirectly by way of other sub-factors as described above. One can see from this the importance of self-esteem in the relationship between stress and comprehensive well-being. Based on these results, the researchers discussed the implications and limitations of this study.