Skin erythema has been widely used as a diagnostic parameter in dermatology. This study describes a methodology for real-time measurement of skin erythema variation induced by negative compression. This study developed an optical measurement probe, which includes a RGB color sensor that translates in the vertical direction, with the magnitude of vertical translation dependening on the amount of skin deformation. Real-time measurement of erythema variation as a function of both negative compression and time was performed in vivo on 10 measurement sites located on the back of each of 12 volunteers who participated in this study. Negative compression was sequentially applied from to and continuously at a constant magnitude () condition. The results showed that skin erythema was uniformly induced at the measurement sites and linearly increased as a function of both negative compression and time. A wide range of individual variation was noted for skin erythema, which may be due to variations in anisotropic skin properties between volunteers. This study demonstrated the clinical feasibility of a novel optical device for skin erythema measurement. Future studies are needed to investigate the clinical applications of this device.