Although much is known about the pathophysiology of severe COVID-19, there are still areas that remain to be determined. It is well established that the pivotal molecular event is a hyperinflammatory response also referred to as a cytokine storm. The aim of this retrospective cohort study was to determine miRNAs which might be predictive for the admission to the intensive care unit (ICU). We analyzed blood samples from 210 COVID-19 patients and the control group consisted of 80 healthy individuals. Results revealed the miRNA expression pattern has the potential to predict the severity of COVID-19, reflecting the clinical symptoms of the infection, such as the need for oxygen therapy and concomitant pneumonia. In particular, low expression of miRNAs miR106a-5p, miR17-5p, miR181a-5p, miR191-5p, miR20a-5p and miR451a, especially in the initial phase of the disease, is associated with an unfavorable clinical course of SARS-CoV-2 infection (admission to the ICU).