COVID-19 patients may manifest thrombocytopenia and some of these patients succumb to infection due to coagulopathy. The aim of our study was to examine platelet count values in patients infected with SARS-CoV-2, comparing them to a control group consisting of non-COVID-19 patients. Moreover, we evaluated the correlation between the platelet value and the respiratory alteration parameters and the outcome (hospitalization and mortality) in COVID-19 patients. The mean platelet values (×109/L) differed between patients with positive or negative SARS-CoV-2 swabs (242.1 ± 92.1 in SARS-CoV-2 negative vs. 215.2 ± 82.8 in COVID-19 patients, p < 0.001). In COVID-19 patients, the platelet count correlated with the A-aO2 gradient (p = 0.001, rho = −0.149), with its increase over the expected (p = 0.013; rho = −0.115), with the PaO2 values (p = 0.036; rho = 0.093), with the PCO2 values (p = 0.003; rho = 0.134) and with the pH values (p = 0.016; rho = −0.108). In COVID-19 negative patients, the platelet values correlated only with the A-aO2 gradient: (p = 0.028; rho = −0.101). Patients discharged from emergency department had a mean platelet value of 234.3 ± 68.7, those hospitalized in ordinary wards had a mean value of 204.3 ± 82.5 and in patients admitted to sub-intensive/intensive care, the mean value was 201.7 ± 75.1. In COVID-19 patients, the survivors had an average platelet value at entry to the emergency department of 220.1 ± 81.4, while that of those who died was 206.4 ± 87.7. Our data confirm that SARS-CoV-2 infection may induce thrombocytopenia, and that the reduction in platelet counts could be correlated with the main blood gas parameters and with clinical outcome; as a consequence, platelet count could be an important prognostic factor to evaluate and stratify COVID-19 patients.