Objectives: Patients arriving in the emergency department (ED) need rapid and reliable evaluation of their respiratory status. Mainstream end tidal carbon dioxide (ETCO2) is one of the methods used for this purpose during general anaesthesia of intubated patients in the operating theatre. Sidestream ETCO2 (SSETCO2) might be a non-invasive, rapid, and reliable predictor of arterial PCO2 in non-intubated patients in respiratory distress. The aim of this study was to verify whether SSETCO2 can accurately predict the arterial PCO2 and to detect variables that may affect this correlation. Methods: A prospective semi-blind study. The participants were 73 patients (47 men, 26 women) referred to the ED for respiratory distress. Arterial blood gas pressures and SSETCO2 measurements were performed and recorded for all patients. Other parameters recorded were: age; body temperature; respiratory rate; blood pressure; pulse rate; and medical diagnosis. Results: A significant correlation was found between SSETCO2 and arterial PCO2 (r = 0.792). Compared with the correlation curve of the whole group, age under 50 years deflected the correlation curve to the left, while temperature above 37.6°C deflected it to the right. The rest of the parameters had no clear influence on the SSETCO2/PCO2 correlation curve. Conclusions: There is a good correlation between SSETCO2 and arterial PCO2 in the ED setting. Young age may increase the arterial PCO2/SSETCO2 gradient while raised temperature may decrease this gradient. Further studies are needed to confirm these findings in the normal healthy population.