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OBJECTIVE Evaluate the clinical utility of the systemic inflammatory response syndrome (SIRS) criteria in dogs and cats presenting to an emergency room (ER). DESIGN Prospective and retrospective observational study, conducted from November 2019 to February 2020. SETTING Small animal university teaching hospital. ANIMALS Prospective enrollment of 1143 dogs and 384 cats consecutively presenting to the ER. Retrospective enrollment of 65 healthy dogs and 57 healthy cats consecutively presenting to the primary care (PC) service. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Positive SIRS-3 status was defined as meeting ≥2 of 3 (dogs) or 3 of 3 (cats) of the vital parameter SIRS criteria (temperature, heart rate, and respiratory rate). Positive SIRS-4 status was defined as meeting ≥2 of 4 (dogs) and ≥3 of 4 (cats) of the vital parameter and CBC SIRS criteria. For each species, proportions of SIRS-positive animals were compared between the ER and PC groups. Clinical outcomes were compared between SIRS-positive and SIRS-negative patients presenting to ER. The number of SIRS-3-positive dogs was statistically but not clinically different between the ER (69.9%) and PC (53.8%) groups (P = 0.009). Overall survival rate was 83% for SIRS-3-positive and 89% for SIRS-3-negative dogs presented to ER (P = 0.007). The number of SIRS-3-positive cats did not differ between ER and PC groups (P > 0.999). Overall survival rate was 61.1% for SIRS-4-positive and 86.8% for SIRS-4-negative cats presented to ER (P = 0.012). CONCLUSIONS Fulfilling the SIRS criteria is common in dogs and rare in cats regardless of presenting service. Meeting SIRS criteria on ER presentation carries a weak negative survival association in dogs and a moderate negative survival association in cats. This study demonstrates that the SIRS criteria have poor discriminatory ability to differentiate healthy from diseased patients and lacks a strong outcome correlation in small animal patients.