Natural convection and entropy generation due to the heat transfer and fluid friction irreversibilities in a three-dimensional cubical cavity with partially heated and cooled vertical walls has been investigated numerically using the finite volume method. Four different arrangements of partially active vertical sidewalls of the cubical cavity are considered. Numerical calculations are carried out for Rayleigh numbers from (10³ ≤ Ra ≤ 10⁶), various locations of the partial heating and cooling vertical sidewalls, while the Prandtl number of air is considered constant as Pr=0.7) and the irreversibility coefficient is taken as ( φ = 10 − 4 ). The results explain that the total entropy generation rate increases when the Rayleigh number increases. While, the Bejan number decreases as the Rayleigh number increases. Also, it is found that the arrangements of heating and cooling regions have a significant effect on the fluid flow and heat transfer characteristics of natural convection and entropy generation in a cubical cavity. The Middle-Middle arrangement produces higher values of average Nusselt numbers.