To date, recommendations for the implementation of awake prone positioning in patients with hypoxia secondary to SARSCoV2 infection have been extrapolated from prior studies on respiratory distress. Thus, we carried out a systematic review and metaanalysis to evaluate the benefits of pronation on the oxygenation, need for endotracheal intubation (ETI), and mortality of this group of patients. We carried out a systematic search in the PubMed and Embase databases between June 2020 and November 2021. A randomeffects metaanalysis was performed to evaluate the impact of pronation on the ETI and mortality rates. A total of 213 articles were identified, 15 of which were finally included in this review. A significant decrease in the mortality rate was observed in the group of pronated patients (relative risk [RR] = 0.69; 95% confidence interval [CI]: 0.480.99; p = 0.044), but no significant effect was observed on the need for ETI (RR = 0.79; 95% CI: 0.631.00; p = 0.051). However, a subgroup analysis of randomized clinical trials (RCTs) did reveal a significant decrease in the need for this intervention (RR = 0.83; 95% CI: 0.710.97). Prone positioning was found to significantly reduce mortality, also diminishing the need for ETI, although this effect was statistically significant only in the subgroup analysis of RCTs. Patients’ response to awake prone positioning could be greater when this procedure is implemented early and in combination with noninvasive mechanical ventilation (NIMV) or highflow nasal cannula (HFNC) therapy.