Moisture and soluble salts are the main causes of degradation of mural paintings, in particular, frescoes. Water is the 'driving force' of damage such as the detachment of the painted layer and the whitening of the painting due to the crystallization of salts (efflorescence). Indeed, the appearance of efflorescence itself is related to the alterations caused by moisture in the process of the evaporation of water through the surface of the wall. Early detection of the presence of moisture under the wall surface is therefore essential for avoiding such kind of damage. In this paper a non-invasive microwave system is described which allows the measurement of the moisture content and the detection of salts in frescoes and mural paintings. The system performs a sub-surface measurement with an investigated depth up to about 2 cm. The measurement system consists of an evanescent-field resonant sensor, a network analyser and a numerical code. The method has been validated by measurements performed on some reference materials with known dielectric characteristics. Several tests on moistened plaster samples, some of them containing calcium nitrate at different concentrations, have been performed in order to verify the effectiveness in quantifying the moisture and salt content. In situ investigations have been carried out by measuring both the moisture content and salt content on frescoes in several museums and churches. The preliminary results prove the usefulness of the method as a diagnostic tool for investigating the health status of frescoes.