In the face of rapid increases in the number of hospitalizations due to COVID-19 in Latin America and the Caribbean, coupled with shortages of human and material resources, including medical equipment and gases, there is a need to redesign models of care in the Region to optimize available resources and ensure that more patients receive the quantity and quality of oxygen they need. Oxygen is included in the World Health Organization’s list of essential medicines and is used to care for patients at all levels of integrated health services networks. The efficacy of oxygen use in the treatment of patients with respiratory conditions caused by COVID-19 has been demonstrated, but there is great opportunity to improve the effectiveness of its use if it is used in a rational, sustainable, and safe way. Bearing in mind that the efficacy of a health technology is measured by its benefit under actual conditions of use, practical actions can be taken to improve the use of medical oxygen and avoid oxygen shortages. A drug is considered to be used rationally when patients receive it according to their clinical needs, in doses appropriate to their individual needs, for an appropriate period, and at a low cost to them and their community. By providing instruction on the rational use of oxygen and promoting it, negative repercussions can be avoided, such as loss of efficacy as a result of activities related to oxygen storage, distribution, and administration. Rational use of oxygen also involves controlling waste due to leaks in storage and distribution systems, use of gas at incorrect pressures, use of incorrectly adjusted flowmeters, and disconnections, among other problems. Another aspect to consider is the provision of adequate technical support for all oxygen production systems, in terms of maintenance and calibration, availability of electrical energy, and specific knowledge about these systems. For these reasons, a set of guidelines has been put together for the development of an efficient management system to deal with situations of oxygen scarcity, both now and in the future.