BACKGROUND: Early sepsis diagnosis is essential to allow timely initiation of adequate care. The TriVerity™ Test, performed on the Myrna™ Instrument, is the first rapid high-multiplex host-response mRNA diagnostic test that supports clinical decision-making by evaluating the likelihood of bacterial and/or viral infections and severity of illness. We present findings of the first, proof of concept, real-world evaluation in an emergency department (ED). METHODS: Blood was collected in PAXgene RESULTS: Among 60 patients, there were 20 (33%) bacterial infections, 15 (25%) viral infections, 11 (18%) bacterial-viral coinfections and 14 (23%) did not have an infection under forced adjudication. Under consensus adjudication, bacterial results demonstrated 95% rule-in specificity and 95% rule-out sensitivity. Viral results demonstrated rule-in specificity 100% and 92% rule-out sensitivity. Since only three patients were admitted to the ICU or died in this cohort, we cannot draw firm conclusions about the predictive value of the test for severe endpoints. CONCLUSIONS: TriVerity is a rapid whole-blood host-response test to reliably detect the presence or absence of bacterial and/or viral infections, as well as to assess illness severity in patients presenting to the ED. Its quick turnaround time aligns with the ED workflow, offering timely insights for clinical decision-making. Results from upcoming large-scale validation studies will provide more detailed results on the diagnostic and prognostic accuracy of the test.