Clinically feasible multiparameter continuous physiological monitoring technologies are needed for use in resource-constrained African healthcare facilities to allow for early detection of critical events and timely intervention for major morbidities in high-risk neonates. We conducted a prospective clinical feasibility study of a novel multiparameter continuous physiological monitoring technology in neonates at Pumwani Maternity Hospital in Nairobi, Kenya. To assess feasibility, we compared the performance of Sibel’s Advanced Neonatal Epidermal (ANNE) technology to reference technologies, including Masimo’s Rad-97 pulse CO-oximeter with capnography technology for heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) measurements and Spengler’s Tempo Easy non-contact infrared thermometer for temperature measurements. We evaluated key performance criteria such as up-time, clinical event detection performance, and the agreement of measurements compared to those from the reference technologies in an uncontrolled, real-world setting. Between September 15 and December 15, 2020, we collected and analyzed 503 h of ANNE data from 109 enrolled neonates. ANNE’s up-time was 42 (11%) h more for HR, 77 (25%) h more for RR, and 6 (2%) h less for SpO2 compared to the Rad-97. However, ANNE’s ratio of up-time to total attached time was less than Rad-97’s for HR (0.79 vs 0.86), RR (0.68 vs. 0.79), and SpO2 (0.69 vs 0.86). ANNE demonstrated adequate performance in identifying high and low HR and RR and high temperature events; however, showed relatively poor performance for low SpO2 events. The normalized spread of limits of agreement were 8.4% for HR and 52.2% for RR and the normalized root-mean-square deviation was 4.4% for SpO2. Temperature agreement showed a spread of limits of agreement of 2.8 °C. The a priori-identified optimal limits were met for HR and temperature but not for RR or SpO2. ANNE was clinically feasible for HR and temperature but not RR and SpO2 as demonstrated by the technology’s up-time, clinical event detection performance, and the agreement of measurements compared to those from the reference technologies.