Burkitt lymphoma (BL) has a tight association with Epstein-Barr virus (EBV), especially in sub-Saharan Africa. While the relationship between BL and EBV is well documented, the relationship between the anti-EBV adaptive immune response, particularly in sub-Saharan African cases, and disease course, has not been substantially investigated. An analysis of T-cell receptor (TCR) complementarity determining region-3 (CDR3) sequences, reported here, from EBV-positive, Ugandan BL tumor samples revealed a correlation between the presence of anti-EBV CDR3s and improved overall survival probabilities. Furthermore, chemical complementarity assessments demonstrated higher complementarity for TCR CDR3s and EBV epitopes in the cases where there had been a detection of the anti-EBV CDR3 AA sequence matches in the BL tumor samples. Overall, the results reported here raise the question of whether EBV targeted immunotherapy would lead to better BL outcomes?