Objectives: To determine the relationship between work related factors and depression among nurses working at Moi Teaching and Referral Hospital. Methods: A cross-sectional design was employed. Stratified sampling technique was used to select 281 participants from the population. A structured questionnaire was used to collect information on the socio-demographic characteristics of the nurses, Beck?s Depression Inventory to assess the symptoms of depression among nurses and Interview Schedules with the heads of nursing departments on factors associated with depression among nurses. STATA version 13 was used to analyze data. Descriptive statistics was used to summarize the data. Bivariate and multivariate statistics was applied to examine relationships between dependent and independent variables. The findings were presented using tables and graphs. The study sought approval by MMUST Institutional Review Board and Institutional Research and Ethics committee of Moi Teaching and Referral Hospital, Moi University School of Medicine. Informed consent of participants was adhered to during the study. Results: Work-related factors had a strong relationship with the depression status, these included education level, department, shift, income and religion. Majority of these variables showed a statistically significant relationship, i.e. education level had a P<0.002, department had a P< 0.014, shift had a P< of 0.013, income P< 0.008, responsibility P< 0.001 while work experience showed an insignificant relationship evidenced by the P<0.553. Conclusion: On the basis of the study findings, the researcher recommends that the policy makers at MTRH should formulate policies that will help prevent depression among nurses and improve service delivery.