Background: Burnout syndrome (BOS) is a serious issue among nurses due to chronic exposure to work‑related stress. Objectives: The aim of this study was to determine the prevalence and associated risk factors of BOS among psychiatric nurses in a hospital in Saudi Arabia. Methods: In this cross‑sectional study, 395 nurses were included through simple random sampling at a psychiatric hospital. The Maslach Burnout Inventory was used to measure the burnout. Multinomial logistic regression was used to determine the factors associated with BOS among nurses. Results: The mean age of the participants was 35.43 ± 7.04 years. Most study participants were married (69.1%) Saudi (74.7%) males (68.4%), and the average time of service in the hospital was 13 years. Most of the participants (82.3%) had burnout, ranging from mild to very severe. After adjustment for covariates, we found that severe BOS was reported among Saudi nurses (odds ratio [OR] 3.28 and confidence interval [CI] 1.28–8.37) and among ex‑smokers (OR 4.9, CI 1.39–17.5). Single participants reported moderate BOS (OR 2.37 and CI 1.19–4.72). These values were statistically significant. Conclusions: BOS is prevalent among psychiatric nurses. The most common factors associated with BOS were Saudi nationality, single status, and being an ex‑smoker. There is a need for counseling services for nurses to address this issue.