The structural stability of a Cu-based metal-organic framework (MOF), subject to different conditions including exposure to ambient air and liquid water, was investigated. A detailed characterization of the substrate was performed using FTIR, XRD, SEM, N2 adsorption, and TGA. Cu3(btc)2 was found to be stable after exposure to ambient air for short periods but undergoes irreversible changes during long-term exposure. These changes are not only manifested in terms of structural modifications as determined by XRD and FTIR data but also suggested by an altered morphology as observed by electron microscopy. Slow hydrolysis reactions initially involving a weakening of the metal-ligand bonds are identified as the main mechanism for the irreversible degradation of the Cu3(btc)2. The length of exposure and the amount of water were found to be the key parameters that determine the stability of the MOF.