BackgroundVeno-arterial carbon dioxide tension difference (ΔPCO2) and mixed venous oxygen saturation (SvO2) have been shown to be markers of the adequacy between cardiac output and metabolic needs in critical care patients. However, they have hardly been assessed in trauma patients. We hypothesized that femoral ΔPCO2(ΔPCO2 fem) and SvO2(SvO2 fem) could predict the need for red blood cell (RBC) transfusion following severe trauma.MethodsWe conducted a prospective and observational study in a French level I trauma center. Patients admitted to the trauma room following severe trauma with an Injury Severity Score (ISS) > 15, who had arterial and venous femoral catheters inserted were included. ΔPCO2 fem,SvO2 femand arterial blood lactate were measured over the first 24 h of admission. Their abilities to predict the transfusion of at least one pack of RBC (pRBCH6) or hemostatic procedure during the first six hours of admission were assessed using receiver operating characteristics curve.Results59 trauma patients were included in the study. Median ISS was 26 (22–32). 28 patients (47%) received at least one pRBCH6and 21 patients (35,6%) had a hemostatic procedure performed during the first six hours of admission. At admission, ΔPCO2 femwas 9.1 ± 6.0 mmHg, SvO2 fem61.5 ± 21.6% and blood lactate was 2.7 ± 1.9 mmol/l. ΔPCO2 femwas significantly higher (11.6 ± 7.1 mmHg vs. 6.8 ± 3.7 mmHg,P= 0.003) and SvO2 femwas significantly lower (50 ± 23 mmHg vs. 71.8 ± 14.1 mmHg,P< 0.001) in patients who were transfused than in those who were not transfused. Best thresholds to predict pRBCH6were 8.1 mmHg for ΔPCO2 femand 63% for SvO2 fem. Best thresholds to predict the need for a hemostatic procedure were 5.9 mmHg for ΔPCO2 femand 63% for SvO2 fem. Blood lactate was not predictive of pRBCH6or the need for a hemostatic procedure.ConclusionIn severe trauma patients, ΔPCO2 femand SvO2 femat admission were predictive for the need of RBC transfusion and hemostatic procedures during the first six hours of management while admission lactate was not. ΔPCO2 femand SvO2 femappear thus to be more sensitive to blood loss than blood lactate in trauma patients, which might be of importance to early assess the adequation of tissue blood flow with metabolic needs.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13049-023-01095-9.