Stress is the body’s reaction to any change that wants an adjustment. The body reacts to the changes i.e physical, mental, and emotional responses. Stress is a part of life. One can experience stress from the environment, body, and thoughts. Even positive life changes such as promotion, mortgage, or the birth of a child produce stress. Materials and methods: The researcher used a Quasi-experimental research approach, a non-randomized control group design. Settings of the study was selected Hospital, a total of 54 mothers were selected by non-probability convenient sampling techniques. The Modified COPE Program was used as an intervention in this study The data obtained were analyzed and interpreted in the light of objectives and hypothesis using both descriptive and inferential statistical in terms of frequency, percentage, and chi-square. Results: The result revealed that the calculated t value of stress (15.010, P=0.05), anxiety (17.779, P=0.05) and coping ability (14.687, P=0.05) is found significant. The results shows that there is a significant relationship between the effect of modified COPE Program with stress, anxiety and Coping ability score of mothers. Hence research hypothesis H2 is accepted. Conclusion: The main focus of the study was to assess the effectiveness of the modified COPE Program on stress, Anxiety, and Coping ability of mothers of premature babies. Mothers are experiencing stress, anxiety, and low coping ability due to a premature baby admitted in NICU. After the implementation of the modified COPE Program mother’s stress and anxiety level decreased gradually and improved coping ability