There have been unprecedented temperature nonuniformities reported in conventional 2D-and emerging 3D-packaged multi-core microprocessors. Therefore, techniques for spatially resolving chip power and temperature profiles in fully operational chips are needed to improve circuit design and enable optimal cooling solutions. This paper presents a high-resolution, infrared (IR) thermography technique for microprocessors operating at fully-operational power levels. A custom, microfluidic heat sink with an IR-transparent working fluid (0.75 LPM) is manufactured to cool an instrumented test chip while permitting optical access for IR thermal imaging. A detailed system calibration is conducted to account for the temperature-dependent optical properties of the chip and heat sink. It is concluded that the IR imaging can be conducted with ~ 0.1 °C error over the temperature range of 45-90 °C if the fluid plenum height is less than 500 μm. For a 2 mm channel, the error can be as high as 43°C due to strong signal attenuation in the fluid.