Background: Burnout is a global phenomenon that is common among health care workers more-so nurses due to the numerous stressors and the high demands associated with the profession. Burnout does not only negatively affect nurses but also patients and healthcare institutions. Objectives: The study assessed the prevalence and factors predicting burnout among nurses in Homa-Bay County Teaching & Referral Hospital (HCTRH), Homa-Bay County, Kenya. The primary outcome was burnout scores and the secondary outcomes are the predictor factors of burnout. Methods: We recruited 104 participants for this cross-sectional descriptive study. A simple random sampling method was applied to allocate the participants from the sampling frame made of 140 nurses. A self-administered questionnaire with four sections on demographic characteristics, professional characteristics, individual characteristics of the participants and the Maslach Burnout Inventory (MBI) was used. The response rate was 86 nurses (82.7%). The prevalence of burnout was assessed using frequency, while Fisher’s Exact was applied to assess the relationship between dimensions of burnout and the socio-demographic, professional and individual factors. Chi-square test of independence and regression analysis were applied to assess the relationship between burnout and the factors.