To assess the effects of resuscitation with oxygen or room air on the cardiac circulation and the activity of superoxide dismutase (SOD) in a hypoxic newborn piglet model. Methods Newborn piglets(1.6-2.5 kg) were randomly assigned into three groups:control group (n=8) with no hypoxic insult;room air group (n=12) resuscitated with room air for 240 min after 120 min hypoxia;and oxygen group (n=12) resuscitated with 100% oxygen for 30 min followed by 210 min with room air after 120 min hypoxia. Blood gas analysis, blood pressure and hemodynamic parameters were recorded at 0, 10, 30, 60, 120, 180 and 240 min of resuscitation. The activity of superoxide dismutase (SOD) in the left ventricle was measured at 240 min of resuscitation using enzyme method . One-way analysis of variance, two-way analysis of variance measured repeatedly and Student-Newman-Keuls test were applied as statistical methods. Results Severe metabolic acidosis, hypotension and hypoxemia were caused by hypoxia.(1)Arterial oxygen partial pressure(PaO2):At 10 min of resuscitation, PaO2 of control group, room air group and oxygen group was (67±4), (78±12) and (409±42)mmHg(1 mmHg=0.133 kPa) (F=580.19, P<0.01). At 30 min of resuscitation, PaO2 of the three group was (68±3), (79±15) and (342±62)mmHg(F=173.67;P<0.01). PaO2 of oxygen group was higher than room air group and control group (10 min:q=42.51 and 39.28, 30 min: q=23.17 and 21.67, all P<0.05). There was no statistical significance between the room air group and control group. (2)Cardiac output(CO):At 240 min of resuscitation,CO of control group, room air group and oxygen group was(181.6±33.8), (150.9±70.1) and (103.6±53.6) dl/(min·kg) (F=4.82, P<0.05). CO of oxygen group was lower than control group (q=4.25,P<0.05). There was no statistical significance between oxygen group and room air group, neither was between room air group and control group (all P>0.05). (3)Arterial oxygen content (CaO2):At 10 min of resuscitation, CaO2 of control group, room air group and oxygen group was(87.0±16.1), (76.9±13.2) and (102.2±15.9) ml O2/dl (F=8.64, P<0.01). At 30 min of resuscitation, CaO2 of the three group was(87.5±14.9), (79.9±11.3) and (100.1±16.7) ml O2/dl (F=5.98, P<0.01). At 10 min of resuscitation, CaO2 of oxygen group was higher than control group and room air group (q=3.14 and 5.85, all P<0.05). At 30 min of resuscitation, CaO2 of oxygen group was higher than room air group (q=4.85, P<0.01), but there was no statistical significance between oxygen group and control group (q=2.71, P>0.05). (4)Oxygen delivery (DO2): At 10, 30, 60, 120, 180 and 240 min of resuscitation, there were no statistical significance among DO2 of control group, room air group and oxygen group [10 min:(16.5±3.3), (15.7±9.9) and (16.9±4.2)L O2/(kg·min), F=0.10;30 min:(16.2±4.1), (15.1±5.5) and (14.5±3.3) L O2/(kg·min), F=0.38;60 min:(16.1±4.2), (14.9±4.0)and(13.3±3.8)L O2/(kg·min), F=1.28;120 min:(15.5±3.7),(15.6±6.1)and(13.4± 4.6) L O2/(kg·min), F=0.66;180 min:(15.4±3.1), (15.3±9.3) and (11.9±5.0) L O2/(kg·min), F=0.97;240 min:(14.7±3.4), (13.4±6.7) and (9.3±5.2) L O2/(kg·min), F=2.84;all P>0.05]. (5) SOD activity in the left ventricle:At 240 min of resuscitation, SOD activity of control group (n=6), room air group (n=8) and oxygen group (n=8) was (289±107), (210±75) and (142±61)U/mg protein, F=5.75, P<0.05]. SOD activity of oxygen group was lower than control group (q=4.79, P<0.01). There was no statistical significance between oxygen group and room air group, neither was between room air group and control group(q=2.58 and 2.39, all P>0.05). Conclusions Despite higher oxygen content in the blood, resuscitation with oxygen is not beneficial to recovery from metabolic acidosis in newborn hypoxic piglets. Oxygen supplementation does not increase oxygen delivery but reduces SV compared to resuscitation with room air. Resuscitation with oxygen may impair the oxidative stress defense.