BACKGROUND: Cancer-related fatigue is widely prevalent in cancer patients and affects quality of life in advanced cancer patients. Fatigue is caused due to both psychologic distress and physiological sequel following cancer progression and its treatment. In this study, we evaluate the effects of yogic intervention in managing fatigue in metastatic breast cancer patients.METHODS: Ninety-one patients with metastatic breast cancer were randomized to receive integrated yoga program (n = 46) or supportive therapy and education (n = 45) over a 3-month period. Assessments such as perceived stress, fatigue symptom inventory, diurnal salivary cortisol, and natural killer cell counts were carried out before and after intervention. Analysis was done using an intention-to-treat approach. Postmeasures for the above outcomes were assessed using ANCOVA with respective baseline measure as a covariate. RESULTS: The results suggest that yoga reduces perceived stress (P = 0.001), fatigue frequency (P < 0.001), fatigue severity (P < 0.001), interference (P < 0.001), and diurnal variation (P < 0.001) when compared to supportive therapy. There was a positive correlation of change in fatigue severity with 9 a.m. salivary cortisol levels. CONCLUSION: The results suggest that yoga reduces fatigue in advanced breast cancer patients.