Taking into account the gut–lung microbiota axis, the new probiotic treatment methods for COVID-19 are currently being discussed. There are effective medicinal preparations of domestic manufacture in the Russian Federation, the immobilized probiotics. The study was aimed to determine the effectiveness of the mixed immobilized probiotic containing the immobilized B. bifidum and lactobacilli L. plantarum (100 million CFU per dose) or the simple immobilized probiotic containing the immobilized B. bifidum (500 million CFU per dose) in the complex therapy of patients with COVID-19. During the open-label, prospective, observational study 70 patients with confirmed diagnosis of COVID-19 received complex treatment which included the immobilized probiotics. All patients were discharged from the hospital with imporoved health status, as well as with improved instrumental and laboratory indicators: body temperature returned to normal in all patients; shortness of breath, cough, feeling of chest tightening, myalgia and headache disappeared; the patients regained sense of smell and taste; the weakness decreased or disappeared (pathognomic symptom for COVID-19). The dynamics of clinical, laboratory and instrumental indicators reflecting the course of the novel coronavirus infection demonstrates the effectiveness of the used complex therapy. The immobilized probiotics may be recommended for the complex treatment of patients with COVID-19.