Background: Breast cancer is the most common cancer among women globally. The emotional and psychological impact of the disease, particularly following mastectomy, can significantly affect quality of life. Objective: This study aimed to assess the effectiveness of box breathing exercises in reducing stress levels among women who have undergone mastectomy. Materials and Methods: A purposive sampling approach was employed, and 140 women, aged 25-65 years, who had undergone mastectomy were selected. Participants were divided into experimental (70 patients) and control (70 patients) groups. The experimental group participated in box breathing exercises, while the control group received routine care. Stress levels were measured using a validated 23-item self-assessment tool, administered at baseline, posttest I, posttest II, and posttest III. Results: The results revealed a significant reduction in stress levels in the experimental group over time. By posttest III, 22.86% of the experimental group attained low stress, while 77.14% showed moderate stress levels. In contrast, the control group remained predominantly in the high-stress category (90%). The differences between the two groups were statistically significant (P < 0.001). Conclusion: Box breathing exercises are an effective, noninvasive intervention for reducing stress in breast cancer patients following mastectomy. Further research is warranted to explore long-term outcomes and the broader applicability of this intervention in various healthcare settings.