Nitric oxide regulates neutrophil migration and alveolar macrophage functions such as cytokine synthesis and bacterial killing, both of which are impaired in immune paralysis associated with critical illness. The aim of this study was to determine whether nitric oxide is involved in immune paralysis and whether exhaled nitric oxide measurement could help to monitor pulmonary defenses. Nitric oxide production (protein expression, enzyme activity, end-products and exhaled NO measurements) was assessed in rats after cecal ligation and puncture to induce a mild peritonitis (leading to ~20% mortality rate). An early and sustained decrease in exhaled nitric oxide was found after peritonitis (from 1 hour to 72 hours) as compared to healthy rats (median [25^th -75^th percentile], 1.5 ppb [1.2-1.7] versus 4.0 ppb [3.6-4.3], p<0:05), despite increased nitric oxide synthase 2 and unchanged nitric oxide synthase 3 protein expression in lung tissue. Nitric oxide synthase 2 activity was decreased in lung tissue. Nitrites/nitrates in supernatants of isolated alveolar macrophages decreased after peritonitis as compared to healthy rats, and an inhibitory experiment suggested arginase overactivity in alveolar macrophages by-passing the nitric oxide substrate. Administration of the nitric oxide synthase 2 inhibitor aminoguanidine to healthy animals reproduced the decreased neutrophil migration toward alveolar spaces that was observed after peritonitis, but L-arginine administration after peritonitis failed to correct the defect of neutrophil emigration despite increasing exhaled NO as compared to D-arginine administration (4.8 [3.9-5.7] versus 1.6 [1.3-1.7] ppb, respectively, p<0.05). In conclusion, the decrease in exhaled nitric oxide observed after mild peritonitis could serve as a marker for lung immunodepression.