The purpose of this study was to determine the effects of smoke induced acute lung injury (S-ALI), extracorporeal membrane oxygenation (ECMO) and transfusion on oxidative stress and plasma selenium levels. Forty ewes were divided into (i) healthy control (. n=. 4), (ii) S-ALI control (. n=. 7), (iii) ECMO control (. n=. 7), (iv) S-ALI. +. ECMO (. n=. 8) and (v) S-ALI. +. ECMO. +. packed red blood cell (PRBC) transfusion (. n=. 14). Plasma thiobarbituric acid reactive substances (TBARS), selenium and glutathione peroxidase (GPx) activity were analysed at baseline, after smoke injury (or sham) and 0.25, 1, 2, 6, 7, 12 and 24. h after initiation of ECMO. Peak TBARS levels were similar across all groups. Plasma selenium decreased by 54% in S-ALI sheep (1.36. ±. 0.20 to 0.63. ±. 0.27. μmol/L, p<. 0.0001), and 72% in sheep with S-ALI. +. ECMO at 24. h (1.36. ±. 0.20 to 0.38. ±. 0.19, p<. 0.0001). PRBC transfusion had no effect on TBARS, selenium levels or glutathione peroxidase activity in plasma. While ECMO independently increased TBARS in healthy sheep to levels which were similar to the S-ALI control, the addition of ECMO after S-ALI caused a negligible increase in TBARS. This suggests that the initial lung injury was the predominant feature in the TBARS response. In contrast, the addition of ECMO in S-ALI sheep exacerbated reductions in plasma selenium beyond that of S-ALI or ECMO alone. Clinical studies are needed to confirm the extent and duration of selenium loss associated with ECMO.