Evidence indicates that oxidative stress generation may contribute to health effects associated with particulate matter (PM) exposure. We investigated oxidative stress markers in 113 workers exposed to metal-rich PM and 61 nonexposed comparable volunteers. The plasma levels of soluble NOX2-derived peptide (sNOX2-dp) and two oxidative stress markers, urinary 8-hydroxydeoxyguanosine (8-OHdG) and 8-iso-prostaglandinF2alpha (8-iso-PGF2α), were analyzed. The plasma levels of the antioxidant alpha-tocopherol were also evaluated. The workers' average exposure to PM with an aerodynamic diameter <10 μm (PM₁₀) was much higher at the workplace than in the city, where the volunteers lived. Workers had significantly higher urinary 8-iso-PGF2α and 8-OHdG and plasma sNOX2-dp levels than nonexposed subjects. Alpha-tocopherol was much lower in workers compared with nonexposed subjects. In multivariable regression models adjusted for age, body mass index, and smoking, 8-iso-PGF2α increased in workers in association with PM10 and metal exposure; 8-OHdG and sNOX2-dp were associated only with iron. Alpha-tocopherol was inversely associated with each of the oxidative stress markers. Our observation leads to the hypothesis that the enhancement of oxidative stress markers associated with exposure to high metal-rich PM levels represents a possible step in the pathways leading from particle exposure to systemic (e.g., cardiovascular) effects.