Summary/Abstract Shock physiology, from any cause, is characterized by an inability to deliver sufficient oxygen to the tissues to meet cellular metabolic demands. Unfortunately, tools that assess the adequacy of oxygen delivery in neonatal critical care patients are often invasive, imprecise, intermittent, and may be misleading. For example, a patient with significant microvascular shunting may exhibit a falsely reassuring arterial oxyhemoglobin saturation or normal lactic acid levels. Still, early identification of the shock state is critical to the appropriate triage, resuscitation, and treatment of patients. Here, we propose the advanced development and testing of an optical probe that monitors peripheral tissue oxygenation as a marker of systemic hemodynamics with strong correlation to central venous oxygen saturation. Local, capillary-ShbO2 (called StO2), primarily reflects the venous or post-O2 extraction compartment of the vasculature and, thus, reflects the adequacy of oxygen delivery to tissues. Changes to systemic blood supply, for example due to bleeding, infection, or low cardiac output may not change arterial oxygen saturation, but are quickly reflected in peripheral StO2 as total oxygen delivery is reduced or peripheral capillaries are shunted to maintain systemic perfusion. We have developed a method for measuring StO2 based on resonance Raman Spectroscopy (RRS). RRS takes advantage of resonant enhancement of the vibrational spectra from hemoglobin when excited using a low power laser near a strong absorption peak (405nm). Thus, the StO2 measurement can be taken against a tissue background and is insensitive to factors such as subcutaneous fat and skin color. Using a prototype device in animal models, we have demonstrated the utility and feasibility of measuring StO2 from the esophagus as a predictor of decompensation due to hemorrhage. In addition, we confirmed the safety of long term use of the device. Here, we propose improvements to our sensor which will enable measurements in a wider range of tissues and will prepare us to begin clinical trials in a neonatal critical care patient population.