This paper proposes a differential sensor based on a pair of open split ring resonators (OSRR) operating in reflection. The output signal is thus the differential reflection coefficient of both resonators, intimately related to their dielectric loading. Thus, for identical loads in both sensing resonators, the individual reflection coefficients are equal, thereby providing an ideally null output signal. By contrast, when unequal dielectric loads truncate the symmetry, the reflection coefficients are different, resulting in a differential output signal related to the level of asymmetry. In order to ease the measurement of the output signal, a rat-race hybrid coupler is used. The OSRR sensing loads are connected to the coupled ports of the hybrid coupler, whereas the input signal is injected to the Δ-port, and the output signal is collected at the isolated port (Σ-port). By this means, the output signal, i.e. the differential reflection coefficient between both sensing loads, is obtained from the transmission coefficient of a simple two-port structure. For experimental validation purposes, the sensor is applied to the measurement of isopropanol content in aqueous solutions, and for that purpose, the sensitive regions are equipped with microfluidic channels.