The Jundiaí-Potengi Estuary (JPE) on the semi-arid coast of Brazil is influenced by multiple sources of pollution. Sediment quality at 10 JPE sites was evaluated through an integrated approach. Rainy and dry seasons were considered. Collected sediments were analyzed for texture, metal, nitrogen, phosphorus concentrations, and toxicity to invertebrates. Geochemical and ecotoxicological data were integrated using qualitative approaches and multivariate techniques. We observed decreased sediment quality in both seasons, particularly in the mid-estuary. In the dry season, the contamination-toxicity relationship was clearer, as hydrological conditions favor contaminant retention within the estuary. Rainy season conditions were found to be worse, since stormwater drainage from agricultural and urban areas carries the contamination into the estuary. Because of the contamination sources and dissolved and particle-bound metal transport, contamination and toxicity did not correlate as clearly in the rainy season. The results suggest that unmeasured contaminants are contributing to JPE sediment degradation.