Background and objective: Senior nursing students encounter various stressors during their practice in clinical learning environment. Inability to manage these stressors, may affect students' academic achievement and well-being, which in turn put the nursing profession at risk. This study aimed to examine the association between senior nursing students' perceived stress and learning environment in clinical practice and their coping strategies. Methods: Study subject consisted of 400 senior nursing students enrolled in the 4th academic year at Faculty of nursing-Tanta University. Present study used descriptive design. Four tools were used to collect the data: Nursing Students' Perception of Stress in Clinical Practice, Physio-Psycho-Social Response Scale, Coping Strategies Scale, and Dundee Ready Education Environment Measure. Results: Senior nursing students' experienced a high level of stress in clinical practice with total mean (2.87), and their response to stress indicated poor health status with total mean (2.76). Their learning environment need more effort to be improved with total mean score (2.4). There were high statistical significant positive correlation between students' perception of learning environment and their responses to stress (p < .001). Conclusions: Senior nursing students experienced high level of stress in clinical practice; their responses to stress indicated a poor health status. Majority of them used problem focused disengagement and emotional focused disengagement strategies to deal with stress in clinical practice. Their perception of learning environment indicated a more positive than negative, so learning environment need more effort to be improved. Accordingly we recommend promote healthy, supportive learning environment and refine nursing curricula.