A novel, noninvasive method for measuring peripheral venous oxygen saturation (Svo2) in newborn infants using near infrared spectroscopy (NIRS) with venous occlusion is described, along with a comparison with co-oximetry of peripheral venous blood. Peripheral Svo2 was measured in 16 newborn infants by NIRS with venous occlusion, and the results were compared with those obtained by co-oximetry of blood from a forearm vein. There was a significant correlation between the two measurements (r = 0.85, p < 0.0001) and close agreement between the two techniques (mean difference (co-oximeter-NIRS) 6%, limits of agreement-5.1% to 17.1%). Three different methods for analysis of the NIRS data were examined to determine which period during the venous occlusion provided the most accurate measurement. The agreement was the same for all methods of analysis.