Abstract Centrifugal pumps are used in many applications in which non-Newtonian fluids are involved: food processing industry, pharmaceutical and oil/gas applications. In addition to pressure and temperature, the viscosity of a non-Newtonian fluid depends on the shear rate and usually is several orders of magnitude higher than water. High values of viscosity cause a derating of pump performance with respect to water. Nowadays, pumping and mixing non-Newtonian fluids is a matter of increasing interest, but there is still lack of a detailed analysis of the fluid-dynamic phenomena occurring within these machines. A specific design process should take into account these effects in order to define the proper pump geometry, able to operate with non-Newtonian fluids with specific characteristics. Only few approaches are available for correcting the pump performance based on the Hydraulic Institute method. In this work, an experimental and numerical campaign is presented for a semi–open impeller centrifugal pump elaborating non-Newtonian fluids. An on-purpose test bench was built and used to investigate the influence on pump performance of three different non-Newtonian fluids. Each pump performance test was accompanied by the rheological characterization of the fluid, in order to detect modifications of the rheological phenomena and allow a proper Computation Fluid Dynamics (CFD) modeling. The performance of the machine handling both Newtonian and non-Newtonian fluids are highlighted in relation with the internal flow field.