Musculoskeletal disorders (MSDs) represent one of the most common occupational problems in nursing. MSDs can negatively impact one's quality of life. The aim of the study was to investigate the relationship between MSDs, job demands, and burnout among emergency nurses. The researchers hypothesized that increased job demands were associated with more MSDs and consequently higher levels of burnout. The study was conducted on a convenience sample of 58 nurses working in the emergency departments of Zagazig University Hospital and Al-Ahrar, Hospital Egypt from October to December 2010, using a cross-sectional analytic design. Data were collected using a self-administered questionnaire that included the Standardized Nordic Questionnaire, the Job Content Questionnaire, and the Maslach Burnout Inventory. The results revealed that 32.8% of the nurses were overweight and 17.2% were obese. The most common sites of pain were the neck (67.2%), shoulder (65.5%), and lower back (63.8%). Lower back pain was the most common site affected (72.4%) with a mean 5.1 on a scale ranging from 0 to 13. A positive correlation existed between the scores of job demand and burnout (r = 0.340, p < 0.01), and the number of reported MSDs with the score of job demand (r = 0.33, p < 0.05). Multiple linear stepwise regression analysis identified the score of job demand and the severity of lower back pain as positive independent predictors of the burnout whereas the job demand score was the independent predictor of the number of MSDs. This study documents an increased prevalence of MSDs among emergency nurses, as predicted by increased job demand and associated with a higher level of burnout. Hence, it is important for hospital and nursing administrators to address the factors contributing to job stress and burnout, with emphasis on job satisfaction and work organization to alleviate the burden of psychosocial factors in this setting.