A protective cover for a stethoscope with a chestpiece having a generally circular anterior surface which is placed against the skin of a patient during use, a generally circular outer rim, and a posterior surface. The cover is disposable and adapted to be removably secured to the chestpiece such that the cover completely covers the anterior surface and outer rim of the chestpiece, thereby physically isolating the anterior surface from contaminants, and further includes provision for effecting a visual change in the appearance of the cover when the stethoscope is used. The cover is preferably formed of a thin, elastomeric, liquid-impervious material and its appearance changes upon exposure to one or more of moisture, pressure, galvanic skin response and skin temperature.