Estuaries have an essential ecological function for several marine fish species, that use these systems as nurseries. Previous studies in the Gironde estuary have reported an increase in water temperature and an extended seawater intrusion associated to global changes. In this study, we evaluated whether these changes impact the nursery function in the middle part of the system, based on the analyses of long-term data series (1991–2009) collected in that area. Trend analysis, correlations and generalized additive models (GAM) were computed in order to study the influence of water temperature and salinity changes on marine juveniles occurrence/densities. Results showed that densities of all the studied species (i.e. Engraulis encrasicolus, Sprattus sprattus, Dicentrarchus labrax, Solea solea, Argyrosomus regius, Merlangius merlangus) significantly increased over the period considered. Changes in water temperature and seawater intrusion contributed to explain the variability in presence/absence and in densities of the majority of these species. However, the deviance explained by GAM and the relevance of these two explanatory variables differed considerably according to species. For most species, it was suggested that the interaction of these two factors, and their effects on other variables, may explain the increase in abundance in the middle part of the Gironde. The effects of global changes in this estuarine system may favour its nursery function for marine juveniles, but some evidence of effects at a wider scale (community and ecosystem levels) may alter the structure and functioning of this system.