This study examined the mediating effect of self-esteem on the relationship between locus of control and depression among Chinese university students. In all, 457 students (232 men and 225 women) completed measures of locus of control, self-esteem, and depression. Correlational analyses indicated that external locus of control was related to self-esteem and depression, and self-esteem was related to depression. Structural equation modeling analysis showed that self-esteem partially mediated the influence of locus of control on depression. The significance of the results is discussed.