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Background/objectives: Saliva is gaining importance as a diagnostic sample in pigs. The aim of this research was to evaluate a panel of salivary analytes in three porcine diseases and establish predictive models to detect them., Methods: Saliva samples were obtained from healthy pigs ( n = 97) and pigs affected by meningitis due to Streptococcus suis ( n = 118), diarrhea due to enterotoxigenic Escherichia coli (ETEC, n = 77), and porcine reproductive and respiratory syndrome (PRRS, n = 52). The following biomarkers were analyzed: adenosine deaminase (ADA), haptoglobin (Hp), calprotectin (Calp), aldolase, alpha-amylase (sAA), lactate dehydrogenase (LDH), total protein (TP), and advanced oxidation protein products (AOPPs). Predictive models based on binary logistic regression and decision trees combining those analytes for detecting specific diseases were constructed., Results: The results showed a different biomarker profile between the groups. S. suis and ETEC pigs showed higher values of ADA, Hp, Calp, aldolase, sAA, LDH, and TP than healthy pigs. Pigs with PRRS showed higher values of Hp, Calp, sAA, and LDH than healthy animals. The constructed predictive models showed overall accuracies of over 78% and 87% for differentiating ETEC and PRRS, respectively, whereas the models did not accurately predict S. suis infection., Conclusions: Salivary analytes show different changes in pigs depending on the disease, and the combination of these analytes can contribute to the prediction of different diseases. Further studies should be conducted in larger populations to confirm these findings and evaluate their possible practical applications.