Multi-organ (liver, gills, kidney and spleen) histopathology in gobies (Pomatoschistus spp.) together with metal bioaccumulation and sediment contamination levels were studied during 2011–2013 for estuarine environmental risk assessment in the Ibaizabal estuary (SE Bay of Biscay). Results indicate that sediments were moderately-strongly impacted by metals and organic compounds, suggesting that adverse biological effects could be likely. Similar metal bioaccumulation levels and multi-organ histopathological indices were detected in gobies collected along the estuary, indicating a similar affection degree. Accordingly, both metal bioaccumulation levels and histopathological indices decreased in gobies collected in 2013 reflecting a lower impact on fish health status. Liver, gills and kidney presented higher histopathological damage than spleen. Fat vacuolation of hepatocytes, lamellar fusion and melanomacrophage centers were the most prevalent hepatic, branchial and renal alterations, respectively. These histopathological changes may indicate exposure to non-specific toxicants. Nevertheless, the influence of other environmental variables should not be excluded as causative factors. No severe pathological traits were registered in gonads, suggesting undisturbed reproductive status. In conclusion, the use of multi-organ histopathology in gobies in combination with metal bioaccumulation and sediment contamination levels, contribute to a better understanding of sub-lethal effects and a more accurate environmental risk assessment in the Ibaizabal estuary.