Purpose: The purpose of this study was to establish the relationship between cognitive based classroom streaming on students’ self-esteem among secondary school students in Lira district. It specifically analyzed the differences in the level of self-esteem between low and high ability group of students. Methodology: The study adopted quantitative research approach. A cross sectional comparative research survey design was used to compare the level of self esteem between low and high ability group of students. A valid and reliable self-administered questionnaire was used to collect data. A total of 278 students from three secondary schools were selected using systematic random and purposive sampling techniques respectively. Data was coded and analyzed using Statistical Package for Social Scientists (SPSS version 23). The hypothesis was tested using independent sample t-test. Findings: Findings revealed a significant difference in the level of self-esteem (t = 7.68, p<0.01) with high ability group of students scoring higher than low ability group. It was therefore concluded that ability grouping significantly influences students’ self-esteem. Recommendation: The study recommended that: heterogeneous grouping, school family initiative programmes, guidance and counselling services and other co curricular activities be introduced /reinforced in schools to enable students discover their talents, build their esteem and cope with the environment.