Targeted temperature management (TTM) exerts substantial impact on hemodynamic function in out-of-hospital cardiac arrest (OHCA) patients. Whole-body oxygen consumption (VO) and delivery (DO) have not previously been investigated in a clinical setting during TTM at different levels of temperature after OHCA. A substudy of 151 patients randomized at a single center in the TTM-trial, where patients were randomly assigned TTM at 33°C (TTM33) or 36°C (TTM36) for 24 hours. We calculated VO according to the principle of Fick (VO = cardiac output∗arteriovenous oxygen content difference). DO was calculated as cardiac output∗arterial oxygen content. Cardiac output was measured by pulmonary artery catheter with thermodilution. Arteriovenous oxygen content difference was calculated from arterial and mixed venous oxygen saturation and hemoglobin. Oxygen extraction ratio = VO/DO. At 24 hours, the VO was 169 ± 59 mL O per minute in TTM33 and 217 ± 53 mL O per minute in TTM36 (p < 0.0001). During 24 hours of TTM, the overall difference was 53 mL O minute (95% confidence interval [CI]: 31-74, p < 0.0001). After rewarming at 36 and 48 hours, there was no difference in VO between the groups. DO was overall 277 mL O per minute (95% CI: 175-379, p < 0.0001) higher in the TTM36-group during TTM. Oxygen extraction ratio during TTM was not significantly different between the two groups (2% [95% CI: -0.1 to 5, p = 0.09]). VO during the first 36 hours after OHCA correlated significantly with temperature, and VO was 19 mL O per minute lower per degree reduction in temperature (95% CI: 15-22), p < 0.0001. TTM at 33°C compared to 36°C after OHCA is associated with significantly lower VO and DO, however, oxygen extraction ratio was not significantly different. For each degree lower body temperature, the VO fell by 19 mL O per minute.