A sensor mounting system includes a rigid main body portion defining a housing within which is mounted a compression element. In use, the compression element provides a predetermined biasing force to force a sensor against the skin of a subject. A secondary support structure provides an adjustable biasing force to retain the main body portion against the subject. Alternatively, the main body portion may be mounted to a rigid pod with one or more secondary compression elements, with the pod itself retained against the subject. An interface layer extending from the main body portion provides a cushion to improve the comfort of the subject. The interface layer and sensor interface elements may be in the form of fingers to increase contact of the sensor with a selected portion of the subject.