In this paper we report on the fabrication and characterization of a potentiometric biosensor for the detection of triglycerides. This is constituted by a lipase immobilized on a mesoporous Si matrix. Prototypes, realized on 1 × 1 cm n+-type silicon wafers, show a very high enzymatic activity. Moreover the properties of these biosensors have been shown to be stable in a several months time interval, clearly showing their advantages with respect to traditional triglycerides detection systems. The Michaelis Menten curve is obtained to demonstrate the absence of diffusion problems. Potentiometric measurements are also shown.