Stress has been defined as a threat to one’s quality of life and physical and psychological well-being. Nursing students are more likely to suffer from stress due to the nature of their work, which may play a significant role in the development of psychological illnesses specifically depression. Objective: To find the role of perceived stress in depression in trainee nurses in Pakistan. Methods: The correlational research design was used in this study and the sample was selected by using purposive sampling technique. 555 female trainee nurses of age between 19 to 30 years (mean age of 21.41 years; SD= 2.25) participated in this study. Perceived stress was assessed using Urdu version of Perceived Stress Scale, while for Depression, indigenously developed Siddiqui-Shah Depression Scale was utilized. Results: The findings discovered that perceived stress plays a significant role in depression [R2=.30, β= .55, F (1, 553) = 245.54, p<.00]. Conclusions: Globally, Nurses are taken as a vital part to healthcare system, including Pakistan where mental health issues among the population are noteworthy. The study concluded that perceived stress predicts depression among hospital trainee nurses. The findings may also have substantial implications in the imminent interventions to preclude nursing students experience stress and its inverse impacts of psychological nature.