Objective—To determine agreement between indirect measurements of end-tidal partial pressure of carbon dioxide (Petco2) and saturation of hemoglobin with oxygen as measured by pulse oximetry (Spo2) with direct measurements of Paco2 and calculated saturation of hemoglobin with oxygen in arterial blood (Sao2) in conscious healthy and ill foals. Design—Validation study. Animals—10 healthy and 21 ill neonatal foals. Procedures—Arterial blood gas analysis was performed on healthy and ill foals examined at a veterinary teaching hospital to determine direct measurements of Paco2 and Pao2 along with Sao2. Concurrently, Petco2 was measured with a capnograph inserted into a naris, and Spo2 was measured with a reflectance probe placed at the base of the tail. Paired values were compared by use of Pearson correlation coefficients, and level of agreement was assessed with the Bland-Altman method. Results—Mean ± SD difference between Paco2 and Petco2 was 0.1 ± 5.0 mm Hg. There was significant strong correlation (r = 0.779) and good agreement between Paco2 and Petco2. Mean ± SD difference between Sao2 and Spo2 was 2.5 ± 3.5%. There was significant moderate correlation (r = 0.499) and acceptable agreement between Sao2 and Spo2. Conclusions and Clinical Relevance—Both Petco2 obtained by use of nasal capnography and Spo2 obtained with a reflectance probe are clinically applicable and accurate indirect methods of estimating and monitoring Paco2 and Sao2 in neonatal foals. Indirect methods should not replace periodic direct measurement of corresponding parameters.