The double-stage axially split centrifugal pump is widely used in water diversion and water pumping stations due to their ability to deliver at high heads and large flow rate for long running hours. Their flow characteristics can be greatly influenced by the geometry of the channels between the stages, which is a prominent place for irreversible loss to occur. Numerical investigations were extensively carried out and a comparison was drawn between two multistage axially split centrifugal pumps, with different channel designs between its stages. The reliability of the numerical model was confirmed after a good agreement existed between numerical results and the experiments. Subsequently, entropy generation terms were used to evaluate turbulence dissipation to characterize the flow losses. The modified channels had a great effect on reducing swirl near the impeller eye, thereby improving pump head by 12.5% and efficiency by 4.98% at the design condition. They however induced flow impact, causing an unusual separation, which generated high turbulence dissipation at the blade surfaces. The channels and second stage impeller were identified as major areas for selective optimization since their turbulence dissipation was dominant. Consequently, entropy production analysis with computational fluid dynamics could be relied upon to reveal the loss locations for selective optimization in centrifugal pumps.