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In the present work, unsteady flow solved by the Reynolds time-averaged Navier–Stokes equation was investigated to determine the inflow distortion mechanism and the spatial distribution of hydraulic loss in a bidirectional axial flow pumping station (Case 1) based on the entropy production theory. A laboratory-scale performance experiment was also employed for the accuracy verification of the simulation approach, and an axial flow pump with pipe passages (Case 2) accompanying uniform inflow was utilized for analysis comparison. The results show that the non-uniform inflow causes a noticeable reduction in head and efficiency, as high as 27% and 21%, respectively, and the best efficiency point with uniform inflow shifts to the point with a larger flow rate. The axial velocity of the impeller inlet in Case 2 changes more smoothly along the Span compared with that in Case 1, which further indicates a more uniform inflow at the impeller inlet. The total entropy production (TEP) of each domain in Case 1 is always higher than that in Case 2, and the TEP of the whole domain in Case 1 increased by 18.68%, 30.50%, and 29.67% with flow rates of 0.8<i>Q</i>_des, 1.0<i>Q</i>_des, and 1.2<i>Q</i>_des, respectively, compared with that in Case 2. In the inlet passage, the larger TEPR regions in Case 1 are mainly located in the horn passage, which is far away from the inlet side, and are also distributed in the suction side of impeller blades and guide vanes. Therefore, this work may provide an optimal design reference for pumping stations in practical application.