A first approach to a portable and compact device for point-of-care (PoC) early instantaneous detection of anemia is described. This device works directly with whole blood samples relying on hematocrit analysis by means of impedance analysis. This device consists of a custom electronic instrumentation, postprocessing software and plug-and-play disposable sensor. The designed electronics are connected to a remote computer, which allows control of the instrumentation and results displaying with a user friendly software panel. The disposable sensor is based on a low-cost label-free three gold electrode commercial sensor for 50-μL volume samples. Forty-eight whole blood samples, randomly collected from hospitalized patients in Hospital Clínic, were used to validate the device capability for anemia detection. Whole blood samples were distributed in two groups: 10 samples for system calibration, and 38 samples for system validation. To calibrate the device, a complete EIS experiment has been performed to get a full impedance spectrum analysis, defining an accurate frequency working range for hematocrit detection. Afterward, we developed a protocol for instant impedance detection to determine the system detection accuracy, sensitivity, and coefficient of variation. As a result, impedance variations between different samples have been detected with less than 2% accuracy error for both impedance magnitude and phase. A hematocrit detection algorithm, relying on impedance analysis, has been developed based on the previous studies. The response, effectiveness, and robustness of the portable PoC device to detect anemia have been proved with an accuracy error of 1.75% and a coefficient of variation of less than 5%.