In this paper, the periodically unsteady pressure field caused by rotor-stator interaction has been investigated numerically by computational fluid dynamics (CFD) calculation to evaluate the transient pressure variation in a single-blade pump for multiconditions. Side chamber flow effect is also considered for the simulation to accurately predict the flow in a whole-flow passage. The strength of the pressure fluctuation is analyzed quantitatively by defining the standard deviation of the pressure fluctuation of a revolution period. The analysis of the results shows that higher pressure fluctuation magnitudes can be observed near the blade pressure side and high gradients of fluctuation magnitudes can be obtained at the trailing edge near the pressure side of the blade. An asymmetrical distribution of fluctuation magnitudes in the volute domain can be clearly obtained. On the cylindrical surface around the impeller outlet, although the absolute pressure value is higher for the Q = 11 l/s condition, the magnitude distribution of fluctuations is lower, and a relatively symmetrical fluctuation distribution is obtained for the Q = 22 l/s condition when clearly asymmetrical distributions of fluctuation magnitude can be observed for the design point and for large flow rates. Obvious periodicity can be observed for the pressure fluctuation magnitude distribution on the circumference with different radii in the volute domain, and some subpeaks and subvalleys can be found. The effects of unsteady flow in the side chambers on the entire passage flow cannot be neglected for accurately predicting the inner flow of the pump. The results of unsteady pressure fluctuation magnitude can be used to guide the optimum design of the single-blade pump to decrease the hydrodynamic unbalance and to obtain more stable performance of the pump.