Airway obstruction can be life threatening in burn patients and may contribute to pneumonia and barotrauma. A further increase in morbidity and mortality of burn patients occurs with sepsis. The purpose of this study is describe the histopathology of animals with smoke inhalation and bronchial bacterial challenge and to test the hypothesis that inhalation injury and bacterial airway challenge will increase the degree of airway obstruction compared to sheep with inhalation injury alone. Method: Sheep with inhalation injury by cooled cotton smoke (n = 6) and combined inhalation injury and airway challenge with pseudomonas aeruginosa, (5 × 1011 cfu), (n = 7) were studied for 24 hours. Sham, uninjured animals served as controls (n = 7). At sacrifice, lung tissue was systematically sampled for histopathology and assessment of airway obstruction was preformed on masked slides. Results: Bronchial obstruction was significantly greater in the smoke only and smoke plus bacterial challenge groups compared to sham animals, p < 0.05. Mean bronchial obstruction scores were 6.7 ± 2.9, 27.1 ± 16.9 and 36.2 ± 17.4 for sham, smoke only and smoke + bacteria animals, respectively. Comparison in the degree of bronchiolar obstruction showed no difference between the sham and the smoke only group, but animals receiving smoke plus bacteria showed an approximately 5-fold increase in mean bronchiolar obstruction that was significantly greater than the smoke only group (p < 0.05). Parenchymal tissue from the smoke only group showed virtually no difference compared to sham. In the smoke plus bacterial challenge group, the parenchyma showed extensive alveolar edema with neutrophils and many bronchioles collapsed or filled with edema fluid or neutrophils. Conclusions: Smoke plus bacterial challenge produces much greater levels of airway obstruction and much more extensive parenchymal injury as compared to the sham or smoke only animals.