Abstract Magnetic confinement fusion reactors such as the European fusion demonstration reactor (EU DEMO) have a very complex geometry, which makes the modelling of the nuclear analyses rather tedious and time consuming. The Monte Carlo neutron transport code Serpent-2 developed by VTT in Finland, is able to directly import CAD geometry, then is considered an attractive alternative to the Monte Carlo N-Particle Transport code (MCNP) for its application on fusion reactors. In the first step, a comparison activity is carried out to benchmark the Serpent-2 with MCNP calculations. Both Serpent-2 and MCNP are used to perform the 3D Monte Carlo neutron and photon coupled transport making use of the EU-DEMO BL2017 model and a grid discrete volume source. A very useful conversion tool (called csg2csg) developed by UKAEA researchers was used to translate the MCNP input model to the Serpent-2 input model. The nuclear performance of the EU DEMO Helium Cooled Pebble Bed breeding blanket, such as tritium breeding ratio (TBR), neutron and photon flux spectra, and nuclear heating are analyzed, and the corresponding results are compared between Serpent-2 and MCNP. This study shows that Serpent-2 is suitable for the application of nuclear analysis for the EU DEMO HCPB breeding blanket.