In the present study, the compressive strength, thermal properties and microstructure of self-compacting concrete with different amounts of CuO nanoparticles have been investigated. CuO nanoparticles with an average particle size of 15 nm were added to self-compacting concrete and various properties of the specimens were measured. The results indicate that CuO nanoparticles are able to improve the compressive strength of self-compacting concrete and reverse the negative effects of superplasticizer on compressive strength of the specimens. CuO nanoparticles as a partial replacement of cement up to 4 wt.% could accelerate C–S–H gel formation as a result of the increased crystalline Ca(OH)2 amount at the early ages of hydration. Increasing CuO nanoparticle content to more than 4 wt.%, causes reduced compressive strength because of unsuitable dispersion of nanoparticles in the concrete matrix. Accelerated peak appearance in conduction calorimetry tests, more weight loss in thermogravimetric analysis and more rapid appearance of peaks related to hydrated products in X-ray diffraction results, all indicate that CuO nanoparticles up to 4 wt.% could improve the mechanical and physical properties of the specimens. Finally, CuO nanoparticles improved the pore structure of concrete and caused shifting of the distributed pores from harmless to low harm.