Question: Does supervised physical activity reduce cancer-related fatigue? Design: Systematic review with meta-analysis of randomised trials. Participants: People diagnosed with any type of cancer, without restriction to a particular stage of diagnosis or treatment. Intervention: Supervised physical activity interventions (eg, aerobic, resistance and stretching exercise), defined as any planned or structured body movement causing an increase in energy expenditure, designed to maintain or enhance health-related outcomes, and performed with systematic frequency, intensity and duration. Outcome measures: The primary outcome measure was fatigue. Secondary outcomes were physical and functional wellbeing assessed using the Functional Assessment of Cancer Therapy Fatigue Scale, European Organisation for Research and Treatment of Cancer Quality of Life QUESTIONnaire, Piper Fatigue Scale, Schwartz Cancer Fatigue Scale and the Multidimensional Fatigue Inventory. Methodological quality, including risk of bias of the studies, was evaluated using the PEDro Scale. Results: Eleven studies involving 1530 participants were included in the review. The assessment of quality showed a mean score of 6.5 (SD 1.1), indicating a low overall risk of bias. The pooled effect on fatigue, calculated as a standardised mean difference (SMD) using a random-effects model, was -1.69 (95% CI -2.99 to -0.39). Beneficial reductions in fatigue were also found with combined aerobic and resistance training with supervision (SMD=-0.41, 95% CI -0.70 to -0.13) and with combined aerobic, resistance and stretching training with supervision (SMD=-0.67, 95% CI -1.17 to -0.17). Conclusion: Supervised physical activity interventions reduce cancer-related fatigue. These findings suggest that combined aerobic and resistance exercise regimens with or without stretching should be included as part of rehabilitation programs for people who have been diagnosed with cancer. Registration: PROSPERO CRD42013005803. Keywords: Cancer; Fatigue; Physical exercise.