Carbon sequestration in microporous geological formations is an emerging strategy for mitigating CO2 emissions from fossil fuel consumption. Injection of CO2 in carbonate reservoirs can change the porosity and permeability of the reservoir regions, along the CO2 plume migration path, due to CO2-brine-rock interactions. Carbon sequestration is effectively a microfluidic process over large scales, and can readily benefit from microfluidic tools and analysis methods. In this study, a micro-core method was developed to investigate the effect of CO2 saturated brine and supercritical CO2 injection, under reservoir temperature and pressure conditions of 8.4 MPa and 40 °C, on the microstructure of limestone core samples. Specifically, carbonate dissolution results in pore structure, porosity, and permeability changes. These changes were measured by X-ray microtomography (micro-CT), liquid permeability measurements, and chemical analysis. Chemical composition of the produced liquid analyzed by inductively coupled plasma-atomic emission spectrometer (ICP-AES) shows concentrations of magnesium and calcium in the produced liquid. Chemical analysis results are consistent with the micro-CT imaging and permeability measurements which all show high dissolution for CO2 saturated brine injection and very minor dissolution under supercritical CO2 injection. This work leverages established advantages of microfluidics in the new context of core-sample analysis, providing a simple core sealing method, small sample size, small volumes of injection fluids, fast characterization times, and pore scale resolution.