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Patients with the most severe form of coronavirus disease 2019 (COVID-19) often require invasive ventilation. Determining the best moment to intubate a COVID-19 patient is complex decision and can result in important consequences for the patient. Therefore, markers that could aid in clinical decision-making such as hematological indices are highly useful. These markers are easy to calculate, do not generate extra costs for the laboratory, and are readily implemented in routine practice. Thus, this study aimed to investigate differences in the ratios calculated from the hemogram between patients with and without the need for invasive mechanical ventilation (IMV) and a control group. This was an observational retrospective analysis of 212 patients with COVID-19 that were hospitalized between April 1, 2020 and March 31, 2021 who were stratified as IMV (n = 129) or did not require invasive mechanical ventilation (NIMV) (n = 83). A control group of 198 healthy individuals was also included. From the first hemogram of each patient performed after admission, the neutrophil-to-lymphocyte ratio (NLR), the derived NLR (d-NLR), the lymphocyte-to-monocyte ratio, the platelet-to-lymphocyte ratio, the neutrophil-to-platelet ratio (NPR), and the systemic immune-inflammation index (SII) were calculated. All hematological ratios exhibited significant differences between the control group and COVID-19 patients. NLR, d-NLR, SII, and NPR were higher in the IMV group than they were in the NIMV group. The hematological indices addressed in this study demonstrated high potential for use as auxiliaries in clinical decision-making regarding the need for IMV.