Background: SARS-CoV-2 related pneumonia is characterized by moderate-to severe hypoxemia often associated with hypocapnia the prognostic role of which is poorely documented. Aims: evaluate if hypocapnia can predict the need for non-invasive mechanical ventilation (NIMV) in this setting. Materials and methods: we prospectively studied 52 subjects with moderate-severe SARS-CoV-2 related pneumonia. All the following data were collected at admission to the Emergency Department and processed by univariate and multivariate analysis: clinical and laboratory data, blood gas analysis in room air and lung ultrasound. Results: 33/52 subjects (63,4%) underwent NIMV. At univariate analysis PaCO2 was inversely associated to the need for NIMV (OR 0,82, CI 95% 0,689-0,976, p .025). At multivariate analysis PaCO2 predicted the need for NIMV independently from age, gender, number of comorbidities, d-dimer, CRP, PaO2 and LUS SCORE (OR 0,838, CI 95% 0,710-0,988, p .035). Conclusions: our data suggest that hypocapnia could be an early predictor of clinical worsening in these patients independently from other known predictors of unfavourable outcome, reflecting the occurrence of a deep and frequent respiratory pattern possibly related to the generation of excessive transpulmonary pressure swings leading to a self-induced lung injury (P-SILI). Further studies are needed for validating these data on greater populations.