Normocapnia is suggested for post resuscitation care. For patients with hypercapnia after cardiac arrest, the relationship between rate of change in partial pressure of carbon dioxide (PaCO2) and functional outcome was unknown.This was the secondary analysis of Resuscitation Outcomes Consortium (ROC) amiodarone, lidocaine, and placebo (ALPS) trial. Patients with at least 2 PaCO2 recorded and the first indicating hypercapnia (PaCO2 > 45 mmHg) after return of spontaneous circulation (ROSC) were included. The rate of change in PaCO2 was calculated as the ratio of the difference between the second and first PaCO2 to the time interval. The primary outcome was modified Rankin Score (mRS), dichotomized to good (mRS 0-3) and poor (mRS 4-6) outcomes at hospital discharge. The independent relationship between rate of change in PaCO2 and outcome was investigated with multivariable logistic regression model.A total of 746 patients with hypercapnia were included for analysis, of which 264 (35.4%) patients had good functional outcome. The median rate of change in PaCO2 was 4.7 (interquartile range [IQR] 1.7-12) mmHg per hour. After adjusting for confounders, the rate of change in PaCO2 (odds ratio [OR] 0.994, confidence interval [CI] 0.985-1.004, p = 0.230) was not associated the functional outcome. However, rate of change in PaCO2 (OR 1.010, CI 1.001-1.019, p = 0.029) was independently associated with hospital mortality.For OHCA patients with hypercapnia on admission, the rate of change in PaCO2 was not independently associated with functional outcome; however, there was a significant trend that higher decreased rate was associated with increased hospital mortality.Copyright © 2023 Elsevier Inc. All rights reserved.