Objectives: Lactate clearance (LC) and central venous oxygen saturation (ScvO2) have been proposed as goals of early sepsis resuscitation. The authors sought to determine the agreement and prognostic value of achieving ScvO2 or LC goals in septic shock patients undergoing emergency department (ED)-based early resuscitation. Methods: This was a preplanned analysis of a multicenter ED randomized controlled trial of early sepsis resuscitation targeting three variables: central venous pressure, mean arterial pressure, and either ScvO2 or LC. Inclusion criteria included suspected infection, two or more systemic inflammation criteria, and either systolic blood pressure of <90 mm Hg after intravenous fluid bolus or lactate level of >4 mmol/L. Both ScvO2 and LC were measured simultaneously. The ScvO2 goal was defined as ≥70%. Lactate was measured at enrollment and every 2 hours until the goal was reached or up to 6 hours. LC goal was defined as a decrease of ≥10% from initial measurement. The primary outcome was in-hospital mortality. Results: A total of 203 subjects were included, with an overall mortality of 19.7%. Achievement of the ScvO 2 goal only was associated with a mortality rate of 41% (9/22), while achievement of the LC goal only was associated with a mortality rate of 8% (2/25; proportion difference = 33%; 95% confidence interval [CI] = 9% to 55%). No agreement was found between goal achievement (κ = -0.02), and exact test for matched pairs demonstrated no significant difference between discordant pairs (p = 0.78). Conclusions: No agreement was found between LC and ScvO 2 goal achievement in early sepsis resuscitation. Achievement of a ScvO2≥ 70% without LC ≥ 10% was more strongly associated with mortality than achievement of LC ≥ 10% with failure to achieve ScvO 2≥ 70%.