Ecosystem metabolism is a key ecological attribute and easy to describe, but quantifying metabolism in estuaries is challenging. Properly scaling measurements through time and space requires consideration of hydrodynamics and mixing water from heterogeneous sources, making any estimation uncertain. Here, we compared three methods for modeling ecosystem metabolism in a portion of the Sacramento-San Joaquin Delta. Metabolism estimates based on laboratory incubations, continuous in situ buoys, and an oxygen isotope approach all indicated the system was net heterotrophic, and calculated rates were comparable in magnitude when averaged over the 2-month study. Daily metabolic rates based on in situ buoys were the most variable, likely due to horizontal and vertical advection and poor portrayal of the dissolved oxygen budget. After temporally averaging in situ buoy estimates or smoothing the dissolved oxygen time series for tidal effects, rates were more comparable to the other methods, which may be necessary to account for tidal advection and unbalanced contributions from subhabitats within the metabolic footprint. Incubation-based rates represent the finest temporal and spatial scale and only account for pelagic processes, which may explain why incubation-based rates were lower than the other two methods. The oxygen isotope method provided temporally and spatially integrated rates that were bracketed by the other two methods and may be a valuable tool in systems matching the model requirements. Because uncertainty arises in each method from a number of assumptions and scaling calculations, the resolution of metabolic rates in estuaries is likely coarser and more variable than in other aquatic ecosystems.