The COVID-19 disease has represented one of the most important threats to health. The most severe form is acute respiratory distress syndrome (ARDS). The inflammatory response can cause hematologic changes. To determine the association between the Neutrophil/lymphocyte ratio (NLR) and the mean platelet volume (MPV) associated with mortality in critically ill patients with COVID-19 and ARDS. A retrospective study was carried out in an intensive care unit (ICU) in a public hospital, with patients in critical condition due to COVID-19 and on mechanical ventilation. The clinical characteristics of admission and severity of the disease were recorded. The end point was the ICU discharge condition. 162 subjects were gathered, 103 were men, with a mean age of 54.54 ± 13.53 years. 66.7% died in the ICU. The NLR had an area under the curve (aROC) of 0.62, with a cut-off point for mortality of > 7.04, sensitivity of 94.4%, specificity of 29.63%. The VPM had an aROC of 0.65 with a cut-off point > 9.5, sensitivity of 30.84%, and specificity of 92.59%; finally, the APACHE II had an aROC of 0.67 with a cut-off point > 14, sensitivity of 51.4% and specificity of 80%. The NLR presented an odds ratio (OR) of 5.02, the VPM 2.06 and the APACHE II score 1.16. NLR, MPV, and APACHE II at ICU admission are associated with mortality for critically ill patients with COVID-19.