Abstract Cognitive and behavioral interventions (CBI) have been used for breast cancer patients with various stages of the disease or undergoing different treatments. However, no quantitative review has summarized their efficacy on the side effects of treatment, distress, and quality of life in the acute treatment setting after diagnosis. This meta-analysis synthesizes data from 19 randomized clinical trials in order to: (a) provide an estimation of overall effect of CBI in breast cancer patients during treatment for breast cancer, i.e., neo-adjuvant and adjuvant treatment; (b) provide average effect sizes on side effects of treatment, distress, and quality of life; and (c) test possible moderators of effect size. The results show that CBI yielded a small effect size overall, specifically on general side effects of treatment, nausea, vomiting, distress, and quality of life. Individual and behavioral interventions seem to elicit better results on distress and on general side effects of treatment, respectively. While more studies are needed with regard to specific side effects (i.e., fatigue, pain, and sleep disturbance), the overall results clearly support the use of CBI in breast cancer patients during treatment.