Oxygen-based cues are direct assessments for a wide range of in vivo biological effects, ranging from mitochondrial disease to tissue engineering/regenerative medicine. Existing electrochemical oxygen sensors are permanent systems applicable to short-term intraoperative use; devices are extracted before wound closure. Development of biocompatible oxygen sensors for long-term, post-surgery monitoring are therefore, desirable for clinical trials where objective oxygen measures are lacking. A biodegradable oxygen sensor that can break down into non-toxic components after a targeted lifespan, reducing the risk of chronic inflammatory response frequently observed with permanent devices, is another promising approach to advance the postoperative monitoring of oxygen tension and provide an additional means to monitor a number of diseases and injuries that are transient in nature, such as bone fracture, traumatic brain injury and wound healing. In this dissertation, we improved the current oxygen sensing technology to the point that it could be used for long-term applications, and further developed a biodegradable oxygen sensor along with a transient energy source to support the design of completely biodegradable oxygen sensing systems. Specifically, a biocompatible oxygen sensor, integrated with a customized circuit and an off-the-shelf battery were designed, built and tested. Oxygen levels in mouse gluteus muscle and zebrafish trunk muscle were both investigated to examine the sensor’s ability to monitor dynamic oxygen tension in vivo. In addition, a biodegradable battery featuring long shelf life and stable performance in the presence of changing body conditions was designed, fabricated and examined in vitro. Finally, a completely biodegradable oxygen sensor featuring a Mg-Mo galvanic pair was demonstrated. This approach measures physiological oxygen tension in a transient, harmless manner in the body, while simultaneously acting as a potential energy source for additional devices. Additionally, such sensors may have application in transient monitoring of the environment, such as environmental spills and algal tides.