ObjectiveExposure to ambient PM2.5 and its bound metals poses a risk to health and disease, via, in part, oxidative stress response. A variety of oxidative stress markers have been used as markers of response, but their relevance to environmental exposure remains to be established. We evaluated, longitudinally, a battery of oxidative stress markers and their relationship with the exposure of PM2.5 and its bound metals in a panel of healthy participants. Material and methodsLevels of residence- and personal-based ambient air PM2.5 and its bound metals, as well as of lung function parameters, were assessed in a total of 58 questionnaire-administered healthy never smoker participants (male, 39.7%). Levels of urinary oxidative stress markers, including Nε-(hexanoyl)-lysine (HEL; an early lipid peroxidation product), 4-hydroxynonenal (4-HNE), N7-methylguanine (N7-meG), and 8-hydroxy-2-deoxyguanosine (8-OHdG), plasma antioxidants [superoxide dismutase (SOD) and glutathione peroxidase (GPx), and urinary metals were measured by ELISA, LC-MS, and ICP-MS, respectively. The results of three repeated measurements at two-month intervals were analyzed using the Generalized Estimating Equation (GEE). ResultsAfter adjusting for confounders, residence- and personal-based PM2.5 levels were positively associated with HEL (β = 0.22 and 0.18) and N7-meG (β = 0.39 and 0.13). Significant correlations were observed between personal air PM2.5-Pb and urinary Pb with HEL (β = 0.08 and 0.26). While FVC, FEV1, FEV1/FVC, MMF, and PEFR predicted% were normal, a negative interaction (pollutant*time, P < 0.05) was noted for PM2.5-V, Mn, Co, Ni, Zn, As, and Pb. Additionally, a negative interaction was found for N7-meG (β = −21.35, −18.77, −23.86) and SOD (β = −26.56, −26.18, −16.48) with FEV1, FVC, and PEFR predicted%, respectively. ConclusionThese findings emphasize potential links between environmental exposure, internal dose, and health effects, thereby offering valuable markers for future research on metal exposure, oxidative stress, and health outcomes.