Background: Nurses are at risk for symptoms of compassion fatigue (CF) and burnout (BO). Social support plays an important role in predicting CF and BO. This study was performed to determine the prevalence of the symptoms of CF and BO and the role of perceived social support in predicting these symptoms in Iranian nurses. Materials and Methods: Using a correlational descriptive survey research design, we selected 173 participants among the nurses working in public hospitals of Malayer, Iran. Professional Quality of Life (CF and BO subscales) and Multidimensional Scale of Perceived Social Support (MSPSS) were used for collecting the data. Results: The obtained results indicated that the prevalence of CF and BO symptoms was 45.3% and 15.03%, respectively, in Iranian nurses. Social support (significant other, family, and friends) was negatively correlated to BO (P < 0.01). Also, there was a negative correlation between social support from family and CF (P < 0.01). According to hierarchical multiple regressions, social support from family was the significant predictor to CF (P < 0.005) and BO (P < 0.001) in nurses. Conclusions: Based on the obtained results, some nurses (especially emergency nurses) are at risk for CF and BO and social support negatively correlated to CF and BO in Iranian nurses. It is necessary to develop support systems for nurses who are at risk for CF and BO.