In a method of operating a three-dimensional image sensor according to example embodiments, modulated light is emitted to an object of interest, the modulated light that is reflected from the object of interest is detected using a plurality of depth pixels, and a plurality of pixel group outputs respectively corresponding to a plurality of pixel groups are generated based on the detected modulated light by grouping the plurality of depth pixels into the plurality of pixel groups including a first pixel group and a second pixel group that have different sizes from each other.