The aim was to examine the relationship of serum inflammatory markers to the level of single-breath diffusing capacity of carbon monoxide (TL,CO). A stratified sample (n = 1,121) of a Norwegian general population aged 18-73 yrs was examined. The inflammatory markers measured were calprotectin, a prominent protein in the cytosol fraction of neutrophil granulocytes, and alpha1-antitrypsin (alpha1-AT), the major inhibitor of neutrophil elastase in the lower respiratory system. Both markers have increased circulating levels in the course of an acute inflammatory reaction. Subjects with a TL,CO < 80% of predicted value had a higher level of both alpha1-AT (p = 0.003) and calprotectin (p < 0.03) than those with a TL,CO > 100%. In multiple linear regression analyses, alpha1-AT was still significantly associated with TL,CO after adjusting for sex, age, smoking habits, haemoglobin, carboxyhaemoglobin, forced expiratory volume in one second and alveolar volume. In a similar analysis, no significant overall association was found between calprotectin and TL,CO, but in a stratified analysis, calprotectin was significantly related to TL,CO in females. However, no significant sex interaction in the relationship between the inflammatory markers and TL,COo was found. The findings suggest that increased levels of alpha1-antitrypsin and of calprotectin are risk factors for decreased diffusing capacity of carbon monoxide.