OBJECTIVE: To determine the association between 5-min Apgar score and umbilical cord artery carbon dioxide tension (pCO₂). DESIGN: Observational study. SETTING: European hospital labor wards. POPULATION: Data from 36,432 newborns ≥36 gestational weeks were obtained from three sources: two trials of monitoring with fetal electrocardiogram (the Swedish randomized controlled trial and the European Union Fetal ECG trial) and Mölndal Hospital data. After validation of the acid-base values, 25,806 5-min Apgar scores were available for analysis. METHODS: Validation of the umbilical cord acid-base values was performed to obtain reliable data. 5-min Apgar score was regressed against cord artery pCO₂ in a polynomial multilevel model. MAIN OUTCOME MEASURES: Five-min Apgar score, umbilical cord pCO₂, pH, and base deficit. RESULTS: Overall, a higher cord artery pCO₂ was found to be associated with lower 5-min Apgar scores. However, among newborns with moderate acidemia, lower umbilical cord artery pCO₂ (≤median pCO₂ for the specific cord artery pH) was associated with lower 5-min Apgar scores, with a relative risk of 2.0 (95% confidence interval: 1.4-2.8) for 5-min Apgar scores 0-6. CONCLUSIONS: Metabolic acidosis affects the newborn's vitality more than respiratory acidosis. In addition, elevated levels of pCO₂ may be beneficial for fetuses with moderate acidemia, and thus cord artery pCO₂ is a factor that should be considered when assessing the compromised newborn.