We measured 8-isoprostane, a biomarker of oxidative stress, and prostaglandin (PG) E₂ in exhaled breath condensate in 36 stable and 14 unstable cystic fibrosis (CF) patients, and in 15 healthy age-matched controls. We studied the relationships of these eicosanoids with clinical, radiological, and systemic inflammatory parameters. Compared with controls [15.5 (11.5–17.0) pg/ml] exhaled 8-isoprostane was increased in stable CF patients [30.5 (25.3–36.0) pg/ml, P<0.001]. Unstable CF patients had higher exhaled 8-isoprostane levels [47.5 (44.0–50.0) pg/ml, P<0.001] than stable CF patients. Unlike PGE₂, exhaled 8-isoprostane was negatively correlated with FEV₁ (r=−0.67; P<0.0001; r=−0.63; P<0.02) and Shwachman score (r=−0.43, P=0.012; r=−0.58, P=0.031) and positively correlated with Chrispin-Norman score (r=0.51, P<0.002; r=0.56, P=0.039) in stable and unstable CF patients, respectively. No correlation was observed with C-reactive protein. Compared with controls [41.0 (29.0–50.0) pg/ml], exhaled PGE₂ was also elevated in stable [72.0 (64.3–81.8) pg/ml, P<0.001) and, to a greater extent, in unstable CF patients [83.0 (74.3–91.3) pg/ml, P<0.001). In patients with CF, exhaled 8-isoprostane and PGE₂ could be a useful marker of disease severity.