It is difficult to distinguish coronavirus disease-2019 (COVID-19) from other viral respiratory tract infections owing to the similarities in clinical and radiological findings. This study aims to determine the clinical importance of platelet count and platelet indices in the differentiation of COVID-19 from influenza and the value of these parameters in the differential diagnosis of COVID-19. The medical records of the patients and the electronic patient monitoring system were retrospectively analyzed. Demographic characteristics, admission symptoms, laboratory findings, radiological involvement, comorbidities, and mortality of the patients were recorded. Forty-three patients diagnosed with influenza and 54 diagnosed with COVID-19 were included in the study. The average age of the COVID-19 patients was lower than that of the influenza patients (influenza: 60.5 years, COVID-19: 52.4 years; pp = 0.024),.024), and the male gender was predominant in the COVID-19 group (influenza: 42%, COVID-19: 56%). According to laboratory findings, the mean platelet volume (MPV) and MPV/platelet ratio were statistically significantly lower, whereas the eosinophil count and platelet distribution width levels were significantly higher (p < 0.05) in the COVID-19 group. It was found that the most common symptom in both groups was dyspnea and that the symptom was more prevalent among influenza patients. In the diagnosis of COVID-19, the platelet count and platelet indices are easily accessible, inexpensive, and important parameters in terms of differential diagnosis and can help in the differentiation of COVID-19 from influenza during seasonal outbreaks of the latter. © 2020 Wiley Periodicals LLC.