Sound velocities of diopside liquid were determined at high pressures and temperatures up to 3.8 GPa and 2375 K, using the ultrasonic technique combined with synchrotron X-ray diffraction and imaging in a multianvil apparatus. Our results show that the sound velocity increases with pressure but is nearly independent of temperature. Using a Monte Carlo approach, the measured high-pressure sound velocities combined with ambient-pressure density provide tight constraints for the equation of state of diopside liquid, with a best-fit adiabatic bulk modulus (KS) of 23.8 ± 0.4 GPa and its pressure derivative (KS') of 7.5 ± 0.5. The calculated adiabatic temperature and density profile of diopside liquid suggest that a melt layer with diopside composition in the upper mantle would be gravitationally unstable and start to crystallize from the bottom of the layer during cooling. By comparing our results with previous acoustic measurements on silicate glasses, we demonstrate the important differences in sound velocities between silicate liquids and glasses and conclude that silicate glasses may not work as a good analog material for studying the acoustic properties of silicate liquids, as measurements on unrelaxed glasses do not capture the entropic contribution to the compressional properties of liquids. We modeled velocity reductions due to partial melts in the upper mantle using our results and found that for a given velocity reduction, the deeper the low-velocity region, the larger the melt fraction is required. Using silicate glass data for such estimation would result in a significant underestimation of melt fractions at high pressures.