Psychological distress is a state of emotional suffering characterized by symptoms of depression and anxiety. There is an association between maternal psychological distress and reduced caregiving behavior. Reduced maternal care to babies is also associated with the low self-esteem of the mothers. The study assesses the prevalence of psychological distress and its relationship with self-esteem among nursing mothers attending the immunization clinic in Ekiti State University Teaching Hospital Ado-Ekiti. This is a descriptive cross-sectional study with 458 nursing mothers recruited. A pretested, adapted, structured interviewer-administered questionnaire was used; data were analyzed using SPSS version 25. Descriptive statistics and inferential statistics were done using the Chi-square and the Spearman correlation coefficient. The level of significance was set at p < 0.05. The mean age of the respondents was 31.7±4.8 years, 398 (86.9%) had tertiary education, 440 (96.0%) were married and 15 (3.3%) were single mothers. Sixty-seven (14.6%), 28 (6.1%), and 24 (5.2%) had mild, moderate, and severe psychological disorders, respectively. Those with low and high self-esteem were 222 (48.5%) and 236 (51.5%) respectively. There was a statistically significant relationship between psychological distress and self-esteem with about 29.6% of the variability in psychological distress being explained by self-esteem alone in the nursing mothers (p< 0.01). Stress of child nursing leads to psychological distress for some nursing mothers and this was significantly associated with self-esteem.