With the aim of investigating the influence of guide vane meridians on the external characteristics and internal flow field of the mixed-flow pump device, this research constructed seven guide vane meridians and applied computational fluid dynamic (CFD) and entropy production theory to investigate the spread of hydraulic loss in a mixed-flow pump. As observed, when the guide vane outlet diameter Dgvo decreased from 350 mm to 275 mm, the head and efficiency increased by 2.78% and 3.05% at 0.7 Qdes, respectively. At 1.3 Qdes, when Dgvo increased from 350 mm to 425 mm, the head and efficiency increased by 4.49% and 3.71%, respectively. At 0.7 Qdes and 1.0 Qdes, the entropy production of the guide vane increased with the increase of Dgvo due to flow separation. When Dgvo < 350 mm, at 1.0 Qdes and 1.3 Qdes, entropy production of the outlet channel increased as Dgvo decreased owing to the excessive flow rate, but at 0.7 Qdes, entropy production did not change much. When Dgvo > 350 mm, at 0.7 Qdes and 1.0 Qdes, due to the expansion of the channel section, the flow separation intensified, which resulted in an increase of the entropy production, but the entropy production decreased slightly at 1.3 Qdes. These results provide guidance for improving the efficiency of pumping stations.