Both severe acute respiratory syndrome coronavirus 2 and influenza viruses cause similar clinical presentations. It is essential to assess severely ill patients presenting with a viral syndrome for diagnostic and prognostic purposes. We aimed to compare clinical and biochemical features between pneumonia patients with coronavirus disease 2019 (COVID-19) and H1N1. Sixty patients diagnosed with COVID-19 pneumonia and 61 patients diagnosed with influenza pneumonia were hospitalized between October 2020-January 2021 and October 2017-December 2019, respectively. All the clinical data and laboratory results, chest computed tomography scans, intensive care unit admission, invasive mechanical ventilation, and outcomes were retrospectively evaluated. The median age was 65 (range 32-96) years for patients with a COVID-19 diagnosis and 58 (range 18-83) years for patients with influenza (p = 0.002). The comorbidity index was significantly higher in patients with COVID-19 (p = 0.010). Diabetes mellitus and hypertension were statistically significantly more common in patients with COVID-19 (p = 0.019, p = 0.008, respectively). The distribution of severe disease and mortality was not significantly different among patients with COVID-19 than influenza patients (p = 0.096, p = 0.049).). In comparison with inflammation markers; C-reactive protein (CRP) levels were significantly higher in influenza patients than patients with COVID-19 (p = 0.033). The presence of sputum was predictive for influenza (odds ratio [OR] 0.342 [95% confidence interval [CI], 2.1.130-0.899]). CRP and platelet were also predictive for COVID-19 (OR 4.764 [95% CI, 1.003-1.012] and OR 0.991 [95% CI 0.984-0.998], respectively. We conclude that sputum symptoms by itself are much more detected in influenza patients. Besides that, lower CRP and higher PLT count would be discriminative for COVID-19.