In animal models of influenza, systemic weight loss is the primary indicator of morbidity from infection, which does not assess local lung pathology or the immune response. Here, we used a mouse-adapted pulse-oximeter as a non-invasive clinical readout of lung function during influenza infection in mice, and found direct correlations between oxygen saturation levels and lung pathology, that reflected the morbidity and survival from influenza infection. We found blood oxygen levels to be a more accurate assessment than weight-loss morbidity in predicting lung pathology in hosts infected with different viral doses, and in assessing immune-mediated viral clearance in the lung.