Background: Recent data found a correlation between lymphopenia occurring early during craniospinal irradiation (CSI) and risk of disease recurrence in newly-diagnosed childhood medulloblastoma. ¹ However, the population included patients that received myelosuppressive chemotherapy prior to or during RT. Here we investigate the effect of lymphopenia during RT in patients with newly-diagnosed pediatric medulloblastoma who did not receive myelosuppressive chemotherapy with RT. Procedure: We analyzed 54 patients with newly-diagnosed medulloblastoma (ages 2-21 years) treated between 1997-2013 with CSI. Log-rank tests were used to determine survival differences, and Cox proportional hazards regression was used to assess associations between patient characteristics and lymphopenia with disease recurrence risk. Results: 78% of patients (40/51) had grade ≥3 lymphopenia by RT week 3; 49% (23/47) improved to grade ≤2 lymphopenia by week 5. Similarly, the lowest median absolute lymphocyte count (ALC) occurred during RT week 3. Sixteen of 54 (30%) patients recurred an average of 30.2 months post-diagnosis. There was higher risk of disease recurrence in patients with grade ≥3 lymphopenia during weeks 4 (log-rank p=0.015; Cox p=0.03) and 5 (log-rank p=0.0009; Cox p=0.004) of RT. Recurrence-free survival was lower in patients with ALC Conclusions: Lymphopenia during RT weeks 4 and 5 correlates with increased risk of tumor recurrence in pediatric patients with newly-diagnosed medulloblastoma. Future studies should correlate baseline numbers of tumor-infiltrating lymphocytes with risks of lymphopenia during RT and tumor recurrence.