Barra de Navidad lagoon (BNL) is one of the main coastal wetlands in the coast of the State of Jalisco, Mexico. It is a Ramsar site (wetland of international importance) and has been included among the 81 mangrove sites with biological relevance and ecological rehabilitation needs in Mexico. Although fish fauna composition is well known in BNL, little evidence exists that support seasonal and spatial changes of fish assemblages’ structure. The hypothesis tested in this study was that there are significant seasonal and spatial changes in BNL fish assemblages’ composition which can be explained, at least partially, by changes in salinity, water temperature and sediment’s granulometry. Fish assemblages were sampled monthly from October 2012 to September 2013 at four zones of BNL, using gill nets (7.62 mm stretched mesh). A sample was taken every month in a randomly selected area of each zone. Prior to each sampling operation, water salinity and temperature were measured using an YSI-30 probe. Samples of sediment were collected with a Van Veen grab sampler in three randomly selected points of each zone for granulometry and organic matter analyses. A total of 2 026 individuals belonging to 48 species were collected. Slightly more than 90 % of all caught fish belonged to nine species: Peruvian mojarra (Diapterus brevirostris), Pacific crevalle-jack (Caranx caninus), White mullet (Mugil curema), Blue sea-catfish (Ariopsis guatemalensis), Oval flounder (Syacium ovale), Pacific lined sole (Achirus mazatlanus), Yellowfin mojarra (Gerres simillimus), Pacific bumper (Chloroscombrus orqueta) and Freckled porcupinefish (Diodon holocanthus). Generalized linear models yielded significant differences among zones for the mean abundance of each of these nine species, but only in two cases seasonal differences were significant (D. brevisrostris and C. caninus). Permutational multivariate analysis of variance yielded also significant differences among zones and between seasons for the composition of the fish assemblage. Redundancy analysis using salinity, temperature and percentage mud in sediment as environmental variables, showed that fish assemblage’s composition varies along two main gradients defined by mud fraction of sediments in a small spatial scale (~ 3 km) and salinity in a seasonal scale. Percentage of variation explained by canonical axes was less than 25 %, indicating that other factors could be influencing changes in assemblage composition. As most species appear as juveniles in the lagoon, fluctuations in their abundances could be linked, at least partially, with recruitment events.