Serial examination and direct measurement of intracompartmental pressure (ICP) are suboptimal strategies for the detection of acute compartment syndrome (CS) because they are operator-dependent and yield information that only indirectly reflects intracompartmental muscle perfusion. As a result, instances of unnecessary fasciotomy and unrecognized CS are relatively common. Recently, near-infrared spectroscopy (NIRS)-based systems for compartment monitoring have generated interest as an adjunct tool. Under ideal conditions, NIRS directly measures the oxygenation of intracompartmental muscle (StO₂), thereby obviating the challenges of interpreting equivocal clinical examination or ICP data. Despite these potential advantages, existing NIRS sensors are plagued by technical difficulties that limit clinical utility. Most of these limitations relate to their transcutaneous design that makes them susceptible to both interference from intervening skin/subcutaneous tissue, underlying hematoma, and instability of the skin-sensor interface. Here, we present a flexible, wireless, Bluetooth-enabled, percutaneously introducible intramuscular NIRS device that directly and continuously measures the StO₂ of intracompartmental muscle. Proof of concept for this device is demonstrated in a swine lower extremity balloon compression model of acute CS, wherein we simultaneously track muscle oxygenation, ICP, and compartment perfusion pressure (PP). The observed StO₂ decreased with increasing ICP and decreasing PP and then recovered following pressure reduction. The mean change in StO₂ as the PP was decreased from baseline to 30 mmHg was −7.6%. The mean difference between baseline and nadir StO₂ was −17.4%. Cross-correlations (absolute value) describing the correspondence between StO₂ and ICP were >0.73. This novel intramuscular NIRS device identifies decreased muscle perfusion in the setting of evolving CS.