Scaffolding cells with hydrogels is a promising strategy to treat many tissue injuries and diseases. Observing hydrogel degradation is essential as it correlates to the cell release from the hydrogel. We monitored implanted hydrogel degradation using CEST MRI, with validation using two-color in vivo near-infrared imaging. An excellent correlation was found between these two methods, with gelation as the major decomposing component. The results demonstrate that CEST MRI can serve as a robust tool for monitoring hydrogel degradation in vivo.