This study was conducted to evaluate heavy metals pollution in sediments of the Nile River- Damietta Branch using mathematical models of heavy metal indices (enrichment factor (EF), contamination factor (CF), pollution load index (PLI), degree of contamination (DC) and geo-accumulation index (Igeo)). The results showed that the concentrations of heavy metals in sediment samples, followed the order of Fe> Zn> Pb> Co> Ni> Cu> Mg. The EF for each heavy metal element was calculated relative to the background values after normalization with the Fe element. According to the mean values of EFs, the descending order of heavy metals enrichment in the sediments was: Cd >Fe> Pb > Co > Zn > Ni > Cu (greater to lower). Cd was considered to poses significant to very high enrichment along with the different stations along the study area. In addition, it recorded very high contamination (7.41±0.71) and Igeo mean value (6.50 ± 1.32) along the study area. PLI values varied between 0.813 and 2.331 along the study area with a mean value of 1.338 ± 0.477. This result showed a considerable degree of contamination (mean value =16.442 ± 7.136) along the branch. However, stations 3, 5, 9 and 10 recorded a very high degree of contamination with values (30.901, 33.867, 56.932 and 48.536), respectively. HI values of heavy metal order was: Cd (239.63) > Pb (72.65) > Co (34.732) > Ni (14.457) > Zn (5.952) > Cu (4.719) > Fe (2.896). With respect to human health, Ni, Pb, Cd, Fe, Zn, Cu, and Co were identified as potential contaminants. whereas, Pb, Cd and Cu are classified as non-carcinogenic by Agency for Toxic Substances and Disease Registry.