[en] Background: Inverse associations have been observed between memory performance and blood concentrations of cadmium (Cd) and lead (Pb). Low antioxidant cell activity has also been linked to decline in memory due to aging. However, it has not yet been established whether the heavy metal-memory relationship is mediated by differences in antioxidant activity. Methods: We examined Cd and Pb levels, as well as oxidative stress parameters, in blood samples from 125 older adults (age range 50–82 years). The Counting Span Test (CST) was used to evaluate working memory capacity (WMC). The Monte Carlo Method for Assessing Mediation (MCMAM) was used to analyze the mediation role of antioxidant activity in the heavy metals-memory association. Results: High blood Cd (BCd) concentration alone, and in combination with elevated blood Pb (BPb) concentration, was associated with poor WMC (p ≤ 0.001) and low enzymatic antioxidant defenses (p ≥ 0.006). The variance in WMC accounted for by BCd or by BCd combine with BPb was 20.6% and 18.6%, respectively. The MCMAM revealed that the influence of BCd and BPb concentrations on WMC was mediated by low antioxidant capacity (confidence interval - CI: 0.072 to − 0.064 for BCd; CI: − 0.062 to − 0.045 for BPb). Conclusion: These findings showed Pb and Cd blood concentration in older adults, even at levels below the current recommended threshold, was negatively associated with WMC and that this relationship may be partly mediated by low antioxidant defenses. Knowledge on the environmental factors that negatively influence brain and cognition during aging can help inform public policy strategies to prevent and control the adverse effects of environmental contaminant exposure during aging. - Graphical abstract: Effects of lead and cadmium exposure on working memory performance and the mediation role of oxidative stress. - Highlights: • Poor cognitive outcomes have been associated with heavy metals exposure. • Cadmium alone and combined with lead was associated with poor working memory. • Low antioxidant capacity was associated with both cadmium and lead. • Cadmium and lead influence on memory may be mediated by low antioxidant defenses. • Strategies to prevent and control exposure to heavy metals must be reinforced.