Coronavirus SARS-CoV-2 spread worldwide, causing a respiratory disease known as COVID-19. The aim of the present study was to examine whether Dipeptidyl-peptidase 3 (DPP3) and the inflammatory biomarkers IL-6, CRP, and leucocytes are associated with COVID-19 and able to predict the severity of pulmonary infiltrates in COVID-19 patients versus nonCOVID- 19 patients. 114 COVID-19 patients and 35 patients with respiratory infections other than SARS-CoV-2 were included in our prospective observational study. Blood samples were collected at presentation to the emergency department. 102 COVID-19 patients and 28 non-COVID-19 patients received CT imaging (19 outpatients did not receive CT imaging). If CT imaging was available, artificial intelligence software (CT Pneumonia Analysis) was used to quantify pulmonary infiltrates. According to the median of infiltrate (14.45%), patients who obtained quantitative CT analysis were divided into two groups (> median: 55 COVID-19 and nine non-COVID-19, <= median: 47 COVID-19 and 19 non-COVID-19). DPP3 was significantly elevated in COVID-19 patients (median 20.85 ng/ml, 95% CI 18.34- 24.40 ng/ml), as opposed to those without SARS-CoV-2 (median 13.80 ng/ml, 95% CI 11.30-17.65 ng/ml; p < 0.001, AUC = 0.72), opposite to IL-6, CRP (each p = n.s.) and leucocytes (p < 0.05, but lower levels in COVID- 19 patients). Regarding binary logistic regression analysis, higher DPP3 concentrations (OR = 1.12, p < 0.001) and lower leucocytes counts (OR = 0.76, p < 0.001) were identified as significant and independent predictors of SARS-CoV-2 infection, as opposed to IL-6 and CRP (each p = n.s.). IL-6 was significantly increased in patients with infiltrate above the median compared to infiltrate below the median both in COVID19 (p < 0.001, AUC = 0.78) and in non-COVID-19 (p < 0.05, AUC = 0.81). CRP, DPP3, and leucocytes were increased in COVID-19 patients with infiltrate above median (each p < 0.05, AUC: CRP 0.82, DPP3 0.70, leucocytes 0.67) compared to infiltrate below median, opposite to non-COVID-19 (each p = n.s.). Regarding multiple linear regression analysis in COVID19, CRP, IL-6, and leucocytes (each p < 0.05) were associated with the degree of pulmonary infiltrates, as opposed to DPP3 ( p = n.s.). DPP3 showed the potential to be a COVID-19-specific biomarker. IL-6 might serve as a prognostic marker to assess the extent of pulmonary infiltrates in respiratory patients.