This study investigated heavy metal pollution in sediments of the Rosetta branch of the River Nile of Egypt to quantify the toxic distribution potential of metals into the surrounding environment. Sediment samples were collected at 9 sites during in four seasons. Organic matter and total metal concentrations were determined using loss on ignition and inductively coupled plasma spectrometry, respectively. Principal component analysis has been applied to evaluate the metal sources and the relationships between metals in sediments. Metal concentrations showed the following order: winter > autumn > spring > summer. Mean concentrations of Cu, Zn, Cd, and Pb in sediments were above the average background value of metals in shale. Pb and Cd showed higher enrichment during all seasons at stations N3/N4, Zn at stations N1 to N4, and Cu at stations N6/N8. The variations in heavy metal total concentration and organic matter are due to different input sources, physico-chemical conditions, and adsorption/precipitation/redox conditions in sediments. Mean values of Geo-accumulation index (Igeo) for Fe, Mn, and Cu were below 0 which were classified as unpolluted during spring, summer, and autumn, except Cu increased from unpolluted to moderately polluted during winter. Igeo values for Cd, Pb, and Zn increased from unpolluted–moderately polluted to highly–very highly polluted during autumn and winter. Pollution Load Index was recorded in highest values during winter, especially at Fuwwah/Basioun and in lowest values during summer at after the Edfina Barrage/before Kafer El-Zayat due to industrial/human activities. Both natural and anthropogenic sources contributed to the metal accumulations in sediments, and industrial, agricultural, and municipal sewage effluents discharged from non-point sources may be the main anthropogenic sources for metals in the Rosetta branch.