Background and purpose: The Zayandeh-Rud River is the sole permanent river in the central plateau of Iran. This river has been extensively exposed to sewage and effluent discharge from various point and non-point sources of pollution. Consequently, the sediment quality of the Zayandeh-Rud River was investigated. Materials and Methods: Sediment sampling was conducted in triplicates at six stations along the Zayandeh-Rud River during the spring, summer, autumn, and winter of 2019-2020. The concentrations of lead and cadmium were then determined. Subsequently, the bioaccumulation factor, Mü, ller's geochemical index, contamination factor, contamination degree, modified contamination degree, potential ecological risk index, and pollution load index were calculated. Results: The results indicated that the mean concentrations of cadmium in spring, summer, autumn, and winter were 1. 18, 1. 13, 1. 08, and 0. 54 mg/kg, respectively. Additionally, the mean concentration of lead was 26. 13, 23. 04, 23. 96, and 11. 17 mg/kg, respectively. The ecological risk assessment index revealed that the region was at a moderate ecological risk during spring, summer, and autumn, while during winter, it was at a low ecological risk. Conclusion: A comparison between the mean metal concentrations and the Canadian sediment quality standard values for fresh waters demonstrated that the lead concentration in sediments is lower than the standard value, whereas cadmium exceeds the standard value. These results highlight the pollution status of the river, which is the primary source of freshwater in the central plateau of Iran. Moreover, this study can serve as a basis for implementing policies to mitigate the accumulation of heavy metals in aquatic ecosystems.