Catchment degradation and exposure of acid sulphate soils can affect estuarine water quality, and this can have impacts on the health of estuarine species and adversely affect fishery productivity. In degraded catchments, aluminium (Al) is mobilised from clay minerals following oxidation of acid sulphate soils, and may be harmful to estuarine crustaceans. We tested the acute toxicity and sub-lethal effects of Al for School Prawn (Metapenaeus macleayi), through a series of experiments conducted under normal (pH 8) and acidic (pH 5) conditions. Experimental data were used to examine mortality. Also, histological examination of the gills and hepatopancreas was conducted to determine pathological consequences of exposure to these stressors. School Prawn did not experience mortality in response to acute exposure to Al under normal pH conditions, but mortality and tissue bioaccumulation of Al was greater under acidic conditions, suggesting an interactive effect of both stressors. Histology revealed sub-lethal effects of Al including structural abnormalities in the gills and hepatopancreas, and evidence of viral infection and immune response, particularly at lower pH and higher Al concentrations. These impacts may impede major vital functions such as respiration, osmotic regulation, metabolism and growth of juvenile School Prawn, which could contribute to productivity bottlenecks in degraded estuaries.