Phononic crystals are resonant structures with great potential to be implemented in applications as liquid sensors. The use of the symmetry reduction technique allows introducing relevant transmission features inside bandgaps by creating defect modes in a periodic regular structure. These features can be used as measures to quantify changes in the speed of sound of liquid samples that could be related to the concentration of analytes or the presence of pathogens among other interesting applications. In order to be able to implement this new technology in more challenging applications, such as biomedical applications, it is necessary to have a very precise and accurate measurement. Changes in temperature greatly affect the speed of sound of the liquid samples, causing errors in the measurements. This article presents a phononic crystal sensor that, by introducing additional defect modes, can carry out differential measurements as a temperature compensation mechanism. Theoretical studies using the transmission line model and analytes at various temperatures show that the proposed temperature compensation mechanism enhances the performance of the sensor in a significant way. This temperature compensation strategy could also be implemented in crystals with different topologies.