Purpose: This study is aimed at comparing the level of occupational stress, ways of coping and the quality of life among nurses. Methods: Descriptive explanatory design was used with 278 nurses working in King Abdul Aziz Hospital in Jeddah, Mental Health Hospital in Jeddah, and Dr. Suleiman Fakeeh Hospital in Jeddah. Findings: Psychiatric nurses experience greater occupational stress than general nurses (p = 0.001). There was no statistically significant difference between the psychiatric and general nurses in relation to coping strategies (p = 0.38). Conclusion: Healthcare institutions should adapt stress evaluation and coping models specific to their unit. Practical Implication: Implementation of programs in each healthcare unit to educate nurses how to deal with work stressors and their negative effects.