The aim of the present study was to determine the short-term effects of hyperoxia on respiratory mechanics in mechanically ventilated infant and adult mice. Eight and two week old BALB/c mice were exposed to inspired oxygen fractions (FIO2) of 0.21, 0.3, 0.6, and 1.0, respectively, during 120 min of mechanical ventilation. Respiratory system mechanics and inflammatory responses were measured. Using the low-frequency forced oscillation technique no differences were found in airway resistance between different FIO2 groups when corrected for changes in gas viscosity. Coefficients of lung tissue damping and elastance were not different between groups and showed similar changes over time in both age groups. Inflammatory responses did not differ between groups at either age. Hyperoxia had no impact on respiratory mechanics during mechanical ventilation with low tidal volume and positive end-expiratory pressure. Hence, supplemental oxygen can safely be applied during short-term mechanical ventilation strategies in infant and adult mice.