Background: The SARS-CoV-2 pandemic has challenged the traditional perspectives of health care. The objective of our study was to analyze the association of different hematological biomarkers and respiratory assistance with the disease's severity and mortality in COVID-19.Materials and methods: A single reference center, cross-sectional, retrospective, descriptive and analytical, observational study was carried out on 362 SARS-CoV-2 positive adults from April to October 2020.Results: The mean age of the population was 55.92±13.12 years. A distribution by gender of n=227 (63.0%) men and n=135 women (37.0%) was found. Mortality occurred in 14% of the studied population. Comorbidities associated were hypertension n=128 (35.0%) and diabetes n=112 (31.0%). Of the 362 patients, 64 required advanced ventilatory support when taken to the intensive care unit, of these 39 (60.9%) died and only 25 (39.1%) survived (p<0.0001). On the other hand, biochemical indicators such as CRP, D-dimer, DHL, lymphocytes, leukocytes, neutrophils, and the neutrophil/lymphocyte ratio, showed a significant difference (p<0.0001) at admission and during the stay in the intensive care unit.Conclusions: Patients who required ventilatory assistance showed an increased risk of mortality, as did those who were admitted to the intensive care unit. Higher mortality was associated with higher values of CRP, DHL, D-dimer, neutrophil/lymphocytes ratio, total leukocytes, and lower lymphocytes.