Photoplethysmography (PPG) is a valuable technique for noninvasively evaluating physiological parameters. However, traditional PPG devices have significant limitations in high-motion and low-perfusion environments. To overcome these limitations, we investigated the accuracy of a clinically novel PPG site using SPYDR®, a new PPG sensor suite, against arterial blood gas (ABG) measurements as well as other commercial PPG sensors at the finger and forehead in hypoxic environments. SPYDR utilizes a reflectance PPG sensor applied behind the ear, between the pinna and the hairline, on the mastoid process, above the sternocleidomastoid muscle, near the posterior auricular artery in a self-contained ear cup system. ABG revealed accuracy of SPYDR with a root mean square error of 2.61% at a 70-100% range, meeting FDA requirements for PPG sensor accuracy. Subjects were also instrumented with SPYDR, as well as finger and forehead PPG sensors, and pulse rate (PR) and oxygen saturation (SpO2) were measured and compared at various reduced oxygen profiles with a reduced oxygen breathing device (ROBD). SPYDR was shown to be as accurate as other sensors in reduced oxygen environments with a Pearson's correlation >93% for PR and SpO2. In addition, SPYDR responded to changes in SpO2 up to 50 s faster than PPG measurements at the finger and forehead.