Packed beds of gas-solid systems are extensively used as reactors, separators, dryers, filters, heat exchangers and combustors. The design of packed beds requires a detailed knowledge of local dynamics of flow, composition and temperature. Unfortunately, investigations for the development of 3D modelling codes by computational fluid dynamics are still not sufficiently mature compared with those relying on 2D modelling or simplified pseudo-homogenous models. This project investigates non-uniform catalyst deactivation in packed bed reactors of low aspect ratios under steady-state and dynamic operations. Low aspect ratio packed beds were selected as they are known to generate non-uniform distribution of local flow. Detailed knowledge of flow dynamics in terms of local structure of the packed bed, pressure drops, interstitial flow, heat and mass rate distributions was examined. The discrete element method was used to generate various packing configurations and the results of profiles of porosity were in a good agreement with the semi-analytical models, especially, in the vicinity of the wall. Similar oscillation trends with damping profiles towards the centre of the packed beds were observed. Flow heterogeneity was assessed by tests of mass transfer dispersion through a Lagrangian approach. Interactions of fluid flow, mass and heat transfers, and local deactivation of alumina catalyst Al2O3 of CO oxidation were investigated under design and operating conditions. An increase in the activation energy of deactivation promoted the deactivation by accelerating the reaction rate and releasing additional thermal energy, which in turn accelerated the deactivation. The 3D modelling allowed observation of local catalyst deactivation at packing pore level which is typically not accessible by the 2D modelling or pseudo-homogeneous models. In addition, the deactivation was quite asymmetrical along axial and radial directions, leading to uneven rates of thermal expansion and contraction and causing local deactivation associated with temperature runaways.