This research examined the effects of lecturer-student relationship on the self-esteem and academic performance of nursing students at the University of Cape Coast, Ghana. The descriptive statistics on the level-clustered random samples indicated two of the lecturer-student relationships, more connectedness and non-threatening, to be positive while the other two, independent and conflicting, were negative relationships. Thus the student-lecturer relationship was an average. With the exception of connectedness, where low score showing less connectedness rather resulted in high self-esteem, the rest of the reported lecturer-student relationships correlated in good dimensions with high self-esteem of the students. However, while the association seemed to promote self-esteem, it rather indicated opposite dimension with regard to academic performance with increasing number of years spent in the department. The study revealed that because there was little interaction between lecturers and students resulting in the average relationship, the prevailing relationship did not directly or not strong enough to influence high academic and high level attainment but rather encouraged high self-esteem which in turn stimulated high academic and level attainment significantly (p< 0.01). Hence even-though it is a positive relationship which provides good environment for high academic performance, the reverse is possible especially at the higher education where the long exposure to the socio-cultural practices and the modes of instruction might have had tremendous impact on how students perceive and relate to lecturers in order to enhance their academic performance. We recommend improving student-lecturer relationship to drive self-esteems of students for higher academic performance. It is also suggested that further researches be carried out for modeling, possibly mixed-effects model of the academic performance of students taking into consideration self-esteem, lecturer relationship, socio-cultural and economic factors and other key determinants.