Abstract Occlusion of microorganisms in wastewater particles often governs the overall performance of a disinfection system, and the associated health risks of post-disinfected effluents. Little is currently known on the penetration of chemical oxidants into particles developed in wastewater treatment. In this work, a reactive transport model that incorporates intra- and extra-particle chemical decay, radial intra-particle diffusion, mass transfer resistance at particle surfaces, and non-linear reaction kinetics within a competitive multi-particle size aqueous environment, was used to analyze the penetration of ozone and chlorine into wastewater particles. Individual characteristics from two secondary wastewater treatment facilities were used in model calibration. Simulations revealed that significant ozone transport within particles greater than 6 μm required large initial concentrations to exhaust the preferential reaction with aqueous soluble matter. Chlorinated samples exhibited apparently slower reactions and thus deeper penetration (22–40 μm). Chlorine penetration was less sensitive to variations in the extra-particle reaction and disinfectant concentration than ozone. Model simulations that considered elevated initial concentrations of chemical disinfectants revealed that complete inactivation of all particle size domains was not possible with current disinfection practices (e.g., contact times). Reduction in the health risks associated with wastewater particles requires treatment that efficiently balances particle removal (filtration) and particle inactivation (disinfection).