The present paper deals with entropy generation study of CuO/water nanofluid flow over a spherical heat source that is installed inside a cylindrical channel with sudden expansion and contraction. To estimate the entropy generation rate; first, the governing equations are solved numerically to find the velocity and temperature fields in the domain where the flow is steady and laminar. Next, using the simulation data, the entropy generation number is calculated theoretically. The effects of nanofluid concentration, nanoparticle size, blockage ratio, and Reynolds number on the entropy generation have been investigated. The outcomes of this research elucidate that entropy generation number rises with an increase in the nanoparticle volume fraction and surface temperature of the heat source. On the other hand, it was found that the entropy generation is diminished by implementing finer nanoparticles and lowering the blockage ratio. In this study, a new correlation has also been presented to calculate the Nusselt number that is a function of Reynolds number, Prandtl number, and blockage ratio. (C) 2017 Elsevier Ltd. All rights reserved.