Protected sensor field effect transistors (SFETs). The SFETs include a semiconductor substrate, a field effect transistor, and a sense electrode. The SFETs further include an analyte-receiving region that is supported by the semiconductor substrate, is in contact with the sense electrode, and is configured to receive an analyte fluid. The analyte-receiving region is at least partially enclosed. In some embodiments, the analyte-receiving region can be an enclosed analyte channel that extends between an analyte inlet and an analyte outlet. In these embodiments, the enclosed analyte channel extends such that the analyte inlet and the analyte outlet are spaced apart from the sense electrode. In some embodiments, the SFETs include a cover structure that at least partially encloses the analyte-receiving region and is formed from a cover material that is soluble within the analyte fluid. The methods include methods of manufacturing the SFETs.