The temporal and spatial variability of dissolved inorganic phosphate (DIP), nitrogen (DIN), carbon (DIC) and dissolved organic carbon (DOC) were studied in order to determine the net ecosystem metabolism (NEM) of San Diego Bay (SDB), a Mediterranean-climate lagoon. A series of four sampling campaigns were carried out during the rainy (January 2000) and the dry (August 2000 and May and September 2001) seasons. During the dry season, temperature, salinity and DIP, DIC and DOC concentrations increased from oceanic values in the outer bay to higher values at the innermost end of the bay. DIP, DIC and DOC concentrations showed a clear offset from conservative mixing implying production of these dissolved materials inside the bay. During the rainy season, DIP and DOC increased to the head, whereas salinity decreased toward the mouth due to land runoff and river discharges. The distributions of DIP and DOC also showed a deviation from conservative mixing in this season, implying a net addition of these dissolved materials during estuarine mixing within the bay. Mass balance calculations showed that SDB consistently exported DIP (2.8–9.8 × 10 3 mol P d −1), DIC (263–352 × 10 3 mol C d −1) and DOC (198–1233 × 10 3 mol C d −1), whereas DIN (5.5–18.2 × 10 3 mol N d −1) was exported in all samplings except in May 2001 when it was imported (8.6 × 10 3 mol N d −1). The DIP, DIC and DOC export rates along with the strong relationship between DIP, DIC or DOC and salinity suggest that intense tidal mixing plays an important role in controlling their distributions and that SDB is a source of nutrients and DOC to the Southern California Bight. Furthermore, NEM ranged from −8.1 ± 1.8 mmol C m −2 d −1 in September to −13.5 ± 5.8 mmol C m −2 d −1 in January, highlighting the heterotrophic character of SDB. In order to explain the net heterotrophy of this system, we postulate that phytoplankton-derived particulate organic matter, stimulated by upwelling processes in the adjacent coastal waters, is transported into the bay, retained and then remineralized within the system. Our results were compared with those reported for the heterotrophic hypersaline coastal lagoons located in the semi-arid coast of California–Baja California, and with those autotrophic hypersaline systems found in the semi-arid areas of Australia. We point out that the balance between autotrophy and heterotrophy in inverse estuaries is dependent on net external inputs of either inorganic nutrients or organic matter as it has been indicated for positive estuaries.