The River Nile is the main life artery in Egypt. Recently, concerns have been raised about accumulation of microplastics and polycyclic aromatic hydrocarbons (PAHs) in water, sediments, and aquatic animals' tissue, especially that there are few studies on these points in freshwater. The present study aimed to assess the accumulation of microplastics and polycyclic aromatic hydrocarbons in two freshwater invertebrates with two different modes of feeding (Procambarus clarkii and Anodonta anatine), and evaluate the effect of depuration on them. Samples were collected in summer from the El- Gharbiya region in the Egyptian Delta. The obtained results indicated the occurrence of some microplastics with the abundance of Polyethylene terephthalate (PET). Concerning PAHs, their composition pattern in sediment samples is mainly dominated by four-ring PAHs, whereas low molecular weight PAHs dominated water and invertebrate samples. PAHs levels in invertebrates were significantly higher than those in sediments and water. The highest bioaccumulation was detected in Anodonta anatine. Anthracene, phenanthrene and pyrene accumulation were significantly increased in Procambarus clarkia. However, significant declines were observed in fluorene and naphthalene levels. While, a highly significant decrease at all PAHs levels were observed in Anodonta sp. except for fluorene. Overall, the study detected various microplastic types in the Nile River, including polyamide (PA, nylon), polystyrene (PS), polypropylene (PP), polyethylene terephthalate (PET), high-density polyethylene (HDPE), and cellophane. Additionally, twelve polycyclic aromatic hydrocarbon (PAH) compounds were recorded for accumulation in two invertebrate models. Unfortunately, depuration did not have a significant effect on microplastic accumulation in both bivalves and crayfish, and only a slight effect on some types of polycyclic aromatic hydrocarbons. Urgent and radical solutions are needed to preserve the Nile water, especially since pollutants can be transferred to humans through drinking water or the food chain.