Mortality of planktonic populations is difficult to determine because assumptions of the methods are rarely met, more so in estuaries where tidal exchange ensures violation of the assumption of a closed or spatially uniform population. Estuarine plankton populations undergo losses through movement from productive regions, creating a corresponding subsidy to regions that are less productive. We estimated mortality rates of the copepod Pseudodiaptomus forbesi in the San Francisco Estuary using a vertical-life-table approach with a Bayesian estimation method, combined with estimates of spatial subsidies and losses using a spatial box model with salinity-based boundaries. Data came from a long-term monitoring program and from three sample sets for 1991–2007 and 2010–2012. A hydrodynamic model coupled with a particle-tracking model supplied exchange rates between boxes and from each box to several sinks. In situ mortality, i.e., mortality corrected for movement, was highly variable. In situ mortality of adults was high (means by box and sampling program 0.1–0.9 day −1 ) and appeared invariant with salinity or year. In situ mortality of nauplii and copepodites increased from fresh (~ 0) to brackish water (means 0.4–0.8 day −1 ), probably because of consumption by clams and predatory copepods in brackish water. High mortality in the low-salinity box was offset by a subsidy which increased after 1993, indicating an increase in mortality. Our results emphasize the importance of mortality and spatial subsidies in structuring populations. Mortality estimates of estuarine plankton are feasible with sufficient sampling to overcome high variability, provided adjustments are made to account for movement.