Heavy metals like cadmium (Cd) and lead (Pb) are pollutants that are toxic, difficult to decompose and accumulate in biota. One of the biota that lives in the waters is mullet fish. This fish is demersal, has a relatively long life period, has a specific tolerance to the aquatic environment and highly consumable in Indonesia. Therefore need to know the metal content of Cd and Pb in water, sediments and mullet fish and their relationship in Indonesia. The study used a survey method with purposive random sampling at four stations, three replications. The study was conducted from June to November 2019. Analysis of data was descriptive, F-test and correlation. The results showed that the heavy metal content of Cd and Pb between stations in the water media, sediment and in mullet fish there was a significant difference. The highest Cd and Pb were showed in station III, coming from the oil industry, domestic waste and transportation activities. The heavy metal content of Cd and Pb in water, sediment and mullet fish (Planiliza subviridis) in the Donan River, Cilacap shows results exceeding the allowed threshold and danger to human health.