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To evaluate the effect of supplemental selenium administration on the incidence of ventilator-associated pneumonia (VAP) in critically ill patients.Ninety-nine mechanically ventilated patients were randomized to receive either selenium or isotonic saline infusion for 10 days. The primary endpoint was serum glutathione peroxidase-3 (GPX-3) activity and secondary endpoints were development of VAP or death, ICU stay and vasopressor requirement. Serum concentrations of selenium and GPX-3 were measured on Day-1, Day-4 and Day-10. Chi Square and log-rank analyses were used for statistical analyses and odds ratios were calculated.Serum selenium and GPX-3 activity levels increased steadily in the treatment group within 10 days (P < 0.025), while they remained unchanged in the placebo group. The incidence of VAP was 19.4/1000 days of mechanical ventilation in the placebo group while it was 15.8/1000 ventilated days in the treatment group (P = 0.250). The risk of VAP or death was similar between the treatments and placebo groups.Despite increasing the antioxidant activity, selenium supplementation did not affect the incidence of VAP in critically ill patients. The risk of developing VAP or death within 30 days of ICU admission remained the same in the treatment and the controls.Low plasma selenium concentration is frequently encountered among critically ill patients.Selenium is a cofactor for Glutathione Peroxidase-3 (GPX-3), a major antioxidant of the lungsSelenium administration significantly increased GPX-3 activity levels in plasma.Selenium administration did not affect the frequency of ventilator-associated pneumonia.Selenium supplement did not affect the 30-day mortality either.