Increasing demands for high-performance screw pumps in oil and gas as well as other applications require deep understanding of the fluid flow field inside the machine. Important effects on the performance such as dynamic losses, influence of the leakage gaps and presence and extent of cavitation are difficult to observe by experiments. However, it is possible to study such effects using well-validated computational fluid dynamics models. The novel-structured numerical mesh consisting of a single-computational domain for moving screw pump rotors was developed to allow three-dimensional computational fluid dynamics simulation of such machine possible. Based on finite volume method, the instantaneous mass flow rates, rotor torque, local pressure field, velocity field and other performance indicators including the indicated power were predicted. A calculation model for the bearing friction losses was introduced to account for mechanical losses. The geometry of the inlet and outlet passages and piping system are taken into consideration to evaluate their influences on the pressure distribution and shaft power. The paper also shows the influence of rotor clearances on the pump performance. The computational fluid dynamics model was validated by comparing the numerical results with the measured performance obtained in the experimental test rig through the comprehensive experiment performed for a set of discharge pressures and rotational speeds. Validation includes comparison of mass flow rates, shaft power and efficiency under variety of speeds and discharge pressure. It has been found that the predicted results match well with the measurements. The results also showed that the radial clearances have larger influence on the mass flow rate than the interlobe clearance. The correct design of the flow passages within the screw pump plays significant role in minimizing required power consumption. The analysis presented in this paper contributes to better understanding of the working process inside the screw pump and offers a good reference to improve design and optimize such machines in terms of clearance selection, shape of the ports, piping system, etc. In future, this model will be used for analysis of cavitating flows and determining performance of other multiphase screw pumps.