Approximately 5% of COVID-19 patients will have a severe disease requiring invasive or non-invasive mechanical ventilation. In this conditions, sedatives and analgesics are fundamental to promote tolerance, comfort and synchrony with the mechanical ventilator. High and unusual requirements for sedation, analgesics and neuromuscular blockers have been reported in these patients, contributing to prolonged exposure, a high rate of delirium and prolongation of mechanical ventilation. These factors, added to the progressive shortage of these drugs, a high demand for care and less capacity for personalized attention, have created an adverse scenario for their proper and rational use. This paper proposes different pharmacotherapeutic optimization strategies for a rational management of sedation, analgesia and neuromuscular block in critically ill patients with COVID-19, with the therapeutic alternatives available in Chile.