AbstractBackgroundPyothorax, an accumulation of inflammatory fluid in the pleural space, is often caused by foreign body inhalation in dogs, whereas the etiology in cats can be more difficult to discern.ObjectiveCompare clinical, microbiologic findings, and etiology in cats and dogs with pyothorax.AnimalsTwenty‐nine cats and 60 dogs.MethodsMedical records of cats and dogs diagnosed with pyothorax from 2010 to 2020 were reviewed. Clinical findings, fluid analysis, and microbiologic results were retrieved.ResultsAntimicrobials had been administered to equal proportions of cats and dogs before fluid sampling (45% and 47%). Groups did not differ in age or total protein concentration or percentage neutrophils in pleural fluid, but effusion cell count was significantly higher in cats than in dogs (P= .01). Neutrophils containing intracellular bacteria were identified in more cats (27/29, 93%) than dogs (44/60, 73%;P= .05). Penetrating damage to the thorax was implicated as the cause of pyothorax in equal percentages of cats (76%) and dogs (75%). Etiology could not be determined in 2 cats and 1 dog. Cats had higher numbers of bacterial isolates per patient (median, 3) than dogs (median, 1;P= .01) and anaerobes were isolated more often in cats (23/29, 73%) than in dogs (27/60, 45%;P= .003).Conclusions and Clinical ImportancePyothorax had similar etiologies in cats and dogs. Cats had higher fluid cell counts, higher numbers of bacterial isolates identified per patient, and intracellular bacteria detected more commonly than did dogs.