AbstractThe role of protective immunity to Plasmodium falciparum (Pf) malaria in Burkitt lymphoma (BL) is unknown. We investigated the association between BL and antibodies reactive to SE36 antigen, a recombinant protein based on P. falciparum serine repeat antigen 5 gene, targeted by protective malaria immune responses. Cases were children (0–14 years) enrolled at the Korle‐Bu Teaching Hospital, Accra, Ghana, during 1965–1994 with BL confirmed by histology or cytology (92% of cases). Controls were apparently healthy children enrolled contemporaneous to the cases from the nearest neighbor house to the case house and were age,‐ sex‐frequency‐matched to the cases. Anti‐SE36 IgG antibodies were measured using enzyme‐linked absorbent immunoassays (ELISAs). SE36 titers were estimated by extrapolating ELISA optical density readings to a standard fitting curve. Anti‐SE36 titers were log‐transformed for analysis. Odds ratios (ORs) and two‐sided 95% confidence intervals (95% CIs) were estimated using unconditional logistic regression. The mean log endpoint dilution titers were 0.63 logs lower in cases than in controls (8.26 [SD 1.68] vs. 8.89 [SD 1.75], Student's t‐test, p = 0.019). Lower titers were observed in cases than controls aged 0–4 years (p = 0.05) and in those aged 5–14 years (p = 0.06). Low and medium tertiles of anti‐SE36 IgG antibodies were associated with increased OR for BL ([OR 1.67, 95% CI 1.21–2.31] and [OR 1.33, 95% CI 0.96–1.86], respectively, ptrend = 0.002) in analyses adjusting for age, sex, calendar period and test plate. Our findings suggest that compared to similarly aged children enrolled from the same community, children with BL in Ghana have lower antibodies to SE36 antigen.