The purpose of this study was to compare the cardiopulmonary effects of isoflurane (ISO) and sevoflurane (SEV) in foals. Six healthy 1–3-month-old foals (75–163 kg) that were undergoing two minor orthopedic procedures were randomly anesthetized with ISO or SEV in a crossover design. After induction with the inhalation agent in oxygen, foals were placed in dorsal recumbency and 0.1 mg kg−1 butorphanol was administered IV to provide intraoperative analgesia. A 7 Fr 110 cm triple-lumen balloon catheter was advanced through a 8 Fr introducer in a jugular vein until the balloon was wedged in the pulmonary artery. The lungs of each foal were ventilated to maintain normocapnia. During the period of data collection, there was no surgical stimulation and individual depth of anesthesia was adjusted to maintain a weak palpebral reflex (expired ISO 1.45 ± 0.06%, SEV 2.34 ± 0.14%). Measured parameters for the study included heart rate, direct systemic arterial pressure, central venous pressure, cardiac output, direct pulmonary arterial pressure, pulmonary wedge pressure, arterial and venous pH, HCO3, and O2 and CO2 tensions, tidal volume, minute ventilation, and temperature. Measured parameters were used to calculate systemic vascular resistance, pulmonary vascular resistance, cardiac index, stroke volume, stroke index, arterial and mixed venous oxygen contents, oxygen delivery, oxygen consumption, extraction ratio, shunt fraction, and physiological dead space. Baseline data were recorded at 15 minutes after anesthetic agent was first introduced. Data were recorded every 15 minutes after baseline until 60 minutes, and arterial and mixed venous blood gas samples were collected at baseline, 30 minutes, and 60 minutes. After the final data were collected at 60 minutes, surgery commenced. Data were analyzed for normality, and were compared using a two-way anova and Bonferroni's test. Significant differences between drugs were taken if p = 0.05. No significant differences in any of the measured or calculated parameters were observed between ISO and SEV during this study. Sample data for ranges of mean values included: heart rate (ISO 63–67 beats minute−1, SEV 68–73 beats minute−1), mean arterial pressure (ISO 46–96 mm Hg, SEV 44–83 mm Hg), cardiac index (ISO 93–116 mL kg−1 minute−1, SEV 100–117 mL kg−1 minute−1), mean pulmonary pressure (ISO 10–23 mm Hg, SEV 13–19 mm Hg). Based on the results of this study, both ISO and SEV will provide comparable maintenance of anesthesia in 1–3-month-old foals.