Objective: To provide a novel overview of the literature and to summarize the evidence for the effects of aerobic exercise (AE) on serum biomarkers neuroplasticity and brain repair in survivors of stroke. Data sources: We conducted a systematic review and searched MEDLINE, Embase, and Cochrane CENTRAL using terms related to AE, neuroplasticity, brain repair, and stroke. Study selection: Titles, abstracts, and selected full texts were screened by 2 independent reviewers against the following inclusion criteria: including adult survivors of stroke, completing an AE intervention working within the AE capacity, and measuring at least 1 blood biomarker outcome of interest. Data extraction: Two independent reviewers extracted data and assessed risk of bias using Risk of Bias in Nonrandomized Studies-of Interventions and Cochrane's Risk of Bias 2 tools. Data synthesis: Nine studies (n=215 participants) were included, reporting on the following outcomes: brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), cortisol, interleukin 6, and myeloperoxidase. A single bout of high-intensity interval training significantly increased BDNF, IGF-1, and VEGF levels, and a 40-45-minute, 24-session, continuous 8-week AE training program significantly increased BDNF levels. No significant difference in response to any other AE intervention was found in other serum biomarkers. Conclusions: AE can significantly increase BDNF, IGF-1, and VEGF across different AE protocols in survivors of stroke. However, more research is needed to determine the optimal exercise intensity and modalities, specifically in survivors of acute and subacute stroke, and how this may relate to functional outcomes.