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We present a model to predict the long-term distribution and concentrations of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in estuaries comprising multiple intercommunicated sub-embayments. To that end, a mass balance model including rate constants and time-varying water inputs was designed to calculate levels of these compounds in water and sediment for every sub-embayment. Subsequently, outflows and tidal water exchanges were used to interconnect the different regions of the estuary. To calculate plausible risks to population, outputs of the model were used as inputs in a previously designed model to simulate concentrations of PFOA and PFOS in a sport fish species (Cymatogaster aggregata). The performance of the model was evaluated by applying it to the specific case of San Francisco Bay, (California, USA), using 2009 sediment and water sampled concentrations of PFOA and PFOS in North, Central and South regions. Concentrations of these compounds in the Bay displayed exponential decreasing trends, but with different shapes depending on region, compound, and compartment assessed. Nearly stable PFOA concentrations were reached after 50 years, while PFOS needed close to 500 years to stabilize in sediment and fish. Afterwards, concentrations stabilize between 4 and 23 pg/g in sediment, between 0.02 and 44 pg/L in water, and between 7 and 104 pg/g wet weight in fish, depending on compound and region. South Bay had the greatest final concentrations of pollutants, regardless of compartment. Fish consumption is safe for most scenarios, but due to model uncertainty, limitations in monthly intake could be established for North and South Bay catches. Image 1 • A model to predict the fate and levels of PFOA and PFOS in estuaries is presented. • North, Central, and South regions of San Francisco Bay were assessed. • Decreasing concentrations were predicted in every region, compartment, and compound. • Final concentrations for both compounds were highest in South Bay. • Considering uncertainty, fish consumption might be limited in North and South Bay. [ABSTRACT FROM AUTHOR]