BACKGROUND: Pediatric cancer patients are at high risk for life-threatening infections, therapy associated complications and cancer-related side effects. Exercise is a promising tool to support the immune system and reduce inflammation. The primary objective of this systematic review was to evaluate the effects of exercise interventions in pediatric cancer patients and survivors on the immune system. METHODS: For this systematic review (PROSPERO ID: CRD42021194282) we searched four databases (Medline, the Cochrane Library, ClinicalTrials.gov, SPORTDiscus) in June 2021. Studies with pediatric patients with oncological disease were included as main criterion. Two authors independently performed data extraction, risk of bias assessment, descriptive analysis and a direction ratio was calculated for all immune cell parameters. FINDINGS: Of the 1,448 detected articles, eight studies with overall n = 400 children and adolescents with cancer and n = 17 healthy children as controls aged 4 to 19 years met the inclusion criteria. Three randomized, four non-randomized controlled trials and one case series were analyzed descriptively. The exercise interventions had no negative adverse effects on the immune system. Statistically significant results indicated enhanced cytotoxicity through exercise, while changes in immune cell numbers did not differ significantly. Interventions further reduced days of in-hospitalization and reduced the risk of infections. Several beneficial direction ratios in immune parameters were identified favoring the intervention group. INTERPRETATION: Exercise interventions for pediatric cancer patients and survivors had no negative but promising beneficial effects on the immune system, especially regarding cytotoxicity, but data is very limited. Further research should be conducted on the immunological effects of different training modalities and intensities, during various treatment phases, and for different pediatric cancer types. The direction ratio parameters given here may provide useful guidance for future clinical trials. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021194282, PROSPERO ID CRD42021194282.

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