Health care professions including nursing are ranked among the most stressful jobs. The harmful aspects of this stress can affect the nurses, their families, patients, and health care services. The purpose of this study was to investigate the most important stressors among nurses. This quantitative cross-sectional study was conducted among 225 nurses in Yazd, and data were analyzed with SPSS software. Findings showed that 73.4% of nurses had faced severe stress in the preceding 2 years, and workplace stressors were the most significant factors compared with other sources of stress (mean score of 4.62 on a 7-point Likert scale). Heavy workload (mean: 5.76), insufficient salary (5.67), discrimination (5.56), high expectations (5.48), high degree of responsibility for patients (5.48), and physical atmosphere at the workplace (5.25) were the most important workplace stressors. The results also indicated a significant relationship between the percentage of nurses facing stress in the workplace and gender (P = .037), the type of ward (P = .003), the type of employment (P = .050) and also work experience (P = .020). Findings indicate the necessity of improving the work environment for nurses such as changes in physical work conditions, better salaries and terms of employment, educational programs for stress reduction, and coping techniques.