Acute respiratory insufficiency (ARI) accompanied with hypoxemia and hypercapnia requires oxygen therapy. The helium-oxygen therapy secures from the undesirable effects of oxygen therapy. Earlier we showed that introduction of argon in a breathing mixture (BM) reduces the effect of hypoxia. Purpose of the work is to test the potentiality of BM containing a combination of inert gases to counteract oxygen starvation in acute ARI-provoking experiments with animals. Fourteen Wistar rats with a body mass of 276 ± 14.6 grams were divided into two groups. An integral noninvasive technology was used for real-time assessment of oxygen transport and consumption in each animal. Both the experiment and control animals breathed a mixture with a low O2 and high CO2 concentration. The control animals received a routine therapy by a hyperoxic mixture containing nitrogen and carbon dioxide. The experimental animals were treated with a hyperoxic mixture containing helium and argon, and carbon dioxide to induce hypercapnia. The results demonstrated reliably that the hyperoxic heluim-argon mixture reduces burden on the external respiration and favors oxygen utilization in tissues; however, this happens at the expense of a greater stress to the cardiovascular system. In contrast, the hyperoxic mixture used in the control stressed the external respiration rather than the cardiac muscle.