The present study was aimed to investigate the bioaccumulation and biosedimentation factors of some heavy metals in Tilapia zillii inhabiting Lake Qarun, Egypt during the year, 2015- 2016. Water, sediments and fish samples were collected during the period of study. The present study exhibited that, the higher levels of bioaccumulation and biosedimentation factors were recorded in liver samples except for Mn; gills showed their high accumulation while the lower levels of all studied metals were observed in muscle samples. The results indicated the differences of some heavy metals accumulation in different tissues of fish with an increasing rate in the liver during winter and spring except for Zn that attained the higher level in the liver during autumn for bioaccumulation factor and spring for biosedimentation one. The liver of T. zillii accumulated higher levels of Cd, Cu, Fe and Zn than other organs. The results showed that the bioaccumulation factor of Cd, Fe and Mn in fish organs was greater than biosedimentation factor, and this implies that the fish bioaccumulated these metals from the water. While, biosedimentation factor of copper and zinc in the fishes was higher than bioaccumulation one, and this refers to the fact that the fishes bioaccumulated these metals from the sediment. Histopathologically results showed congestion in the interstitial blood vessel and multifocal necrotic areas in renal tubules. While, vacuolated hepatocytes, dilated central vein, compressed blood sinusoids, and congestion were seen in fish liver. Furthermore, intermuscular edematous areas between the muscle bundles were obvious. The increased rate of bioaccumulation, biosedimentation factors, and histopathological changes in the target organs indicated the high risk to fish health and human consumption. Thus, the current study showed that precautionary measures should be taken to prevent heavy metal pollution in the future.