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Experimental data suggest that zinc, copper, and magnesium are involved in carcinogenesis and atherogenesis. Few longitudinal studies have related these minerals to cancer or cardiovascular disease mortality in a population.Data from the Paris Prospective Study 2, a cohort of 4035 men age 30–60 years at baseline, were used to assess the association between serum zinc, copper, and magnesium and all-cause, cancer, and cardiovascular disease mortality. Serum mineral values measured at baseline were divided into quartiles and classified into low (1st quartile, referent group), medium (2nd–3rd quartiles), and high (4th quartile) values. During 18-year follow up, 339 deaths occurred, 176 as a result of cancer and 56 of cardiovascular origin. Relative risks (RRs) for each element were inferred using Cox's proportional hazard model after controlling for various potential confounders.High copper values (4th quartile) were associated with a 50% increase in RRs for all-cause deaths (RR = 1.5; 95% confidence interval = 1.1–2.1), a 40% increase for cancer mortality (1.4; 0.9–2.2), and a 30% increase for cardiovascular mortality (1.3; 0.6–2.8) compared with low values (1st quartile). High magnesium values were negatively related to mortality with a 40% decrease in RR for all-cause (0.6; 0.4–0.8) and cardiovascular deaths (0.6; 0.2–1.2) and by 50% for cancer deaths (0.5; 0.3–0.8). Additionally, subjects with a combination of low zinc and high copper values had synergistically increased all-cause (2.6; 1.4–5.0) and cancer (2.7; 1.0–7.3) mortality risks. Similarly, combined low zinc and high magnesium values were associated with decreased all-cause (0.2; 0.1–0.5) and cancer (0.2; 0.1–0.8) mortality risks.High serum copper, low serum magnesium, and concomitance of low serum zinc with high serum copper or low serum magnesium contribute to an increased mortality risk in middle-aged men.