In critical care, trauma, or other situations involving reduced lung function, oxygen is given to avoid hypoxia. It is known that under certain conditions and long time (several hours) exposure, oxygen is toxic to the lungs, the possible mechanisms being direct cellular damage or surfactant dysfunction. Our key objective was to investigate possible changes in lung function when exposed to 100% oxygen in the short term (several tidal volumes). We performed mechanical tests on lobar surfaces of excised mammalian lungs inflated with air or 100% oxygen, examining (i) stiffness, (ii) non-linear mechanical response and (iii) induced alveolar deformation. Our results showed that within five tidal volumes of breathing 100% oxygen, lung mechanics are significantly altered. In addition, after five tidal volumes of laboratory air, lung mechanical behavior begins to return to pre-oxygen levels, indicating some reversibility. These significant and short-term mechanical effects of oxygen could be linked to oxygen toxicity.