AbstractTemperature of tissues and organs is one of the first parameters affected by physiological and pathological processes, such as metabolic activity, acute trauma, or infection‐induced inflammation. Therefore, the onset and development of these processes can be detected by monitoring deviations from basal temperature. To accomplish this, minimally invasive, reliable, and accurate measurement of the absolute temperature of internal organs is required. Luminescence nanothermometry is the ideal technology for meeting these requirements. Although this technique has lately undergone remarkable developments, its reliability is being questioned due to spectral distortions caused by biological tissues. In this work, how the use of bright Ag2S nanoparticles featuring temperature‐dependent fluorescence lifetime enables reliable and accurate measurement of the absolute temperature of the liver in mice subjected to lipopolysaccharide‐induced inflammation is demonstrated. Beyond the remarkable thermal sensitivity (≈ 3% °C–1 around 37 °C) and thermal resolution obtained (smaller than 0.3 °C), the results included in this work set a blueprint for the development of new diagnostic procedures based on the use of intracorporeal temperature as a physiological indicator.