We describe a simple method of tracking oxygen in real-time with injectable, tissue-integrating microsensors. The sensors are small (500 μm × 500 μm × 5 mm), soft, flexible, tissue-like, biocompatible hydrogels that have been shown to overcome the foreign body response for longterm sensing. The sensors are engineered to change luminescence in the presence of oxygen or other analytes and function for months to years in the body. A single injection followed by noninvasive monitoring with a hand-held or wearable Bluetooth optical reader enables intermittent or continuous measurements. Proof of concept for applications in high altitude, exercise physiology, vascular disease, stroke, tumors, and other disease states have been shown in mouse, rat and porcine models. Over 90 sensors have been studied to date in humans. These novel tissueintegrating sensors yield real-time insights in tissue oxygen fluctuations for research and clinical applications.