The purpose of this study was to examine meaning in life and life orientation as predictors of self-esteem among first-year undergraduate students of the University of Ibadan in Nigeria. A descriptive cross-sectional survey design was used in conducting the study. 192 students comprising 104 males and 88 females whose ages ranged between 63 and 27 years (M = 17.75, SD = 3.01) participated. Participants responded to items of a structured questionnaire containing the Rosenberg Self-Esteem Scale, the Meaning in Life Questionnaire, the Life Orientation Test-Revised, and demographic information. The results showed significant correlations between self-esteem, presence of meaning, optimism, and pessimism. Presence of meaning, search for meaning, optimism, and pessimism significantly predicted self-esteem (R2 = .24; F(4, 185) = 13.10; p < .01). The results also revealed that female students reported higher self-esteem than male students (t(184) = -3.03, p < .01). The mental well-being of students can be enhanced if procedures like counselling and orientation programs address issues on life meaning and if general future outcome expectations are incorporated into the standard procedure for students in their freshman year.