The high rotational speed of the axial flow blood pump and flow separation of the centrifugal blood pump are the main causes for blood damage in blood pump. The mixed flow blood pump can effectively alleviate the high rotational speed and the flow separation. Based on this, the purpose of this study is to explore the performance of the mixed blood pump with a closed impeller. A mixed flow blood pump with closed impeller was studied by numerical simulation in this paper. The flow field characteristics and the pressure distribution of this type of blood pump were analyzed. The hydraulic performance of the blood pump and the possible damages to red blood cells were also discussed. At last, pump performance was compared with the mixed flow blood pump with semi-open impeller. The results show that the mixed flow blood pump with close impeller studied in this paper can operate safely and efficiently with a good performance. The pump can reach the pressure head of 100 mmHg at 5 L/min mass flow rate. Flow in the blood pump is uniform and no obvious separation or vortex occurs. Pressure distribution in and on the impeller is uniform and reasonable, which can effectively avoid the thrombosis of blood. The average mean value of hemolysis index is 4.99 × 10−4. The pump has a good biocompatibility. Compared with the mixed flow blood pump with semi-open impeller, the mixed flow blood pump with closed impeller has higher head and efficiency, a smaller mean value of hemolysis index prediction, a better hydraulic performance and the ability to avoid blood damage. The results of this study may provide a basis for the performance evaluation of the closed impeller mixed flow blood pump.