Background: Electronic waste recycling processes such as dismantling with rudimentary tools and open-air burning result in the release of several toxic chemicals into the environment. Exposure to these toxic chemical mixtures has been associated with many adverse health outcomes affecting respiratory, cardiovascular, neurological, and reproductive systems. DNA methylation has been associated with exposure to toxic chemicals, including heavy metals in several epidemiological studies. DNA methylation profile due to exposure to toxic chemicals among e-waste recyclers has not been studied.Objective: This study assessed the associations between blood and urine levels of heavy metals; cadmium (Cd), lead (Pb), and arsenic (As) and methylation levels of the LINE1 gene among e-waste and control populations in Ghana.Methods: The study enrolled 100 male e-waste workers and 51 all-male non e-waste workers or controls. Body burden of Cd, Pb and As was measured in blood and urine using Inductively Coupled Plasma Mass Spectrometry, while LINE1 methylation levels were assessed by pyrosequencing of bisulfite-converted DNA extracted from whole blood.Results: There was no significant difference in LINE1 methylation between the e-waste and the non e-waste workers (85.16% ±1.32 vs 85.17% ±1.11, p = 0.950). However, CpG1 showed significantly lower mean methylation among controls, compared to e-waste workers (81.70% ±1.86 vs 82.48% ±2.20, p = 0.034). In linear regression models, blood lead (B-Pb) level was significantly inversely associated with overall LINE1 methylation (β = -0.004; 95%CI: -0.008, -0.0003; p = 0.034). Among e-waste recyclers, collectors showed significantly reduced LINE1 methylation levels (β = -0.889; 95%CI: -1.757, -0.021; p = 0.045). Conclusion: Continuous exposure to Pb may interfere with LINE1 methylation leading to epigenetic alteration, thus serve as an early epigenetic marker for future adverse health outcomes.