OBJECTIVE Superoxide radicals (O2-) are generated during reoxygenation following asphyxia, possibly more when higher concentrations of O2 are used during resuscitation. Superoxide dismutase (SOD) is an antioxidant enzyme, which scavenges O2-. We tested the hypothesis that a single intravenous dose of recombinant human Cu,Zn SOD (rhSOD) could influence microcirculation and biochemical markers of asphyxia in piglets reoxygenated with 21% or 100% O2 after combined cerebral hypoxemia-ischemia-hypercapnia. METHODS Anesthetized newborn piglets were randomized to asphyxia (n = 40) or control (n = 3). Asphyxia was induced by ventilation with 8% O2, adding CO2, and temporary occlusion of both common carotid arteries. After 20 min, 16 piglets received rhSOD 5 mg/kg intravenously and reoxygenation with 21% O2 (rhSOD, 21%; n = 8) or 100% O2 (rhSOD, 100%; n = 8), and 24 piglets received saline and reoxygenation with 21% O2 (21%, n = 13) or 100% O2 (100%, n = 11). The cortical microcirculation was assessed by laser Doppler flowmetry, and glutamate in the striatum and hypoxanthine in the cortex were measured by in vivo microdialysis. RESULTS AND CONCLUSION rhSOD peaked in plasma after 5 min. No rhSOD was detected in brain tissue. There were no significant differences between rhSOD and non-rhSOD groups in any measured variable.