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The analysis and classification of cavitary effusions play a crucial role in determining a patient’s diagnosis and prognosis. This prospective study assed ed the activity of Lactate Dehydrogenase (LDH) and the concentration of Total Protein (TP) in serum, pleural, and peritoneal effusions in dogs and cats. Effusions were categorized into three groups: GI (low protein transudate), GII (high protein transudate), and GIII (exudate) following conventional classification. These groups, irrespective of species, were further divided into NPG (neoplastic) and NNG (non-neoplastic) groups. In dogs, significant differences were observed among groups GI, GII, and GIII in terms of effusion LDH activity/ serum LDH (LDHR), effusion LDH activity, serum TP/effusion TP (TPR), and effusion TP. Increased LDH activity in effusion was associated with the presence of neoplasia. The groups organized based on the etiopathogenesis of the effusion exhibited varying values of serum TP, TPR, LDHR, effusion TP, and LDH activity in the effusion. Conversely, statistical analysis of the data from cats showed no differences between the groups for the parameters evaluated in this study. Compared to conventional classification, Light’s criteria demonstrated greater sensitivity in distinguishing between transudates and exudates and higher specificity in identifying transudates. We propose the use of established biochemical analyses to discern the mechanism of cavitary effusion formation and advocate for LDH activity measurement in effusions as a complementary diagnostic tool for cavitary neoplasms, especially in cases where cytological analysis of the effusion yields inconclusive results. [ABSTRACT FROM AUTHOR]