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Aims: To evaluate the effect of a novel method of practical oxygen therapy on physiological parameters related to survival, weaning weight and preweaning mortality of neonatal piglets under commercial farm conditions. Methods: Piglets from hyperprolific sows born with signs of asphyxia, (n = 109; <6 on a score of respiration, meconium staining and activity) or very low birth weight (VLBW; n = 112; <1.05 kg) were selected for the study. Approximately half of each group (n = 55 VLBW piglets and n = 57 piglets with asphyxia) received 100% oxygen immediately after birth using a specially designed facemask for 45 seconds (VLBW) or 1 minute (asphyxiated). Physiological parameters (peripheral blood oxygen saturation (SpO 2 ) blood glucose concentration and rectal temperature) were measured before oxygen treatment 5 minutes after birth (SpO 2 ) and 24 hours later (SpO 2 , blood glucose concentration, temperature). Weight at birth, at 24 hours and at 21 days of age, preweaning mortality, and estimated colostrum intake were also recorded. Results: A significant treatment effect on SpO 2 was observed (p = 0.013 and p < 0.001 for VLBW and asphyxiated piglets respectively). VLBW and asphyxiated piglets that received oxygen treatment had higher SpO 2 after treatment (measured 5 minutes after birth, 97.7 and 97.8% respectively) compared to immediately after birth (93.3 and 86.8% respectively) while untreated piglets showed no variation. Blood glucose concentrations increased in all piglets between birth and 24 hours of age (p = 0.003 and p < 0.001 for asphyxiated and VLBW piglets respectively) and this was higher in asphyxiated piglets that received oxygen than those that did not (5.6 (SE 0.2) mmol/L; p < 0.05). Estimated colostrum intake was higher in asphyxiated (401.6 (SD 24.4) g/kg) and VLBW (374.9 (SE 23.4 g/kg) piglets that received oxygen than those that did not (273.2 (SE 24.1) g/kg; p < 0.001 and 249.0 (SE 22.5) g/kg; p < 0.001 respectively). Similarly weight at weaning was higher in asphyxiated (5.8 (SE 0.2) kg) and VLBW (4.9 (SE 0.2) kg) piglets that received oxygen therapy than control animals (4.9 (SE 0.2) kg; = 0.005 and 4.1 (SE 0.2) kg; p = 0.008 respectively). Furthermore, oxygen treatment markedly reduced preweaning mortality from 9/52 (17%) untreated to 1/57 (1.7%) oxygen-treated piglets suffering asphyxia at birth (p = 0.006). Conclusions: Oxygen therapy improves physiological and productive parameters in piglets born with signs of asphyxia or VLBW. The incorporation of this strategy as part of the farrowing routine enhances the advantages of rearing hyperprolific sows.