Reefs, mangroves and seagrass biotopes often occur in close association, forming a complex and highly productive ecosystem that provide significant ecologic and economic goods and services. Different anthropogenic disturbances are increasingly affecting these tropical coastal habitats leading to growing conservation concern. In this field-based study, we used a visual census technique (belt transects 50 m x 2 m) to investigate the interactions between fishes and microhabitats at the Mamanguape Mangrove-Reef system, NE Brazil. Overall, 144 belt transects were performed from October 2007 to September 2008 to assess the structure of the fish assemblage. Fish trophic groups and life stage (juveniles and adults) were recorded according to literature, the percent cover of the substrate was estimated using the point contact method. Our results revealed that fish composition gradually changed from the Estuarine to the Reef zone, and that fish assemblage was strongly related to the microhabitat availability, as suggested by the predominance of carnivores at the Estuarine zone and presence of herbivores at the Reef zone. Fish abundance and diversity were higher in the Reef zone and estuary margins, highlighting the importance of structural complexity. A pattern of nursery area utilization, with larger specimens at the Transition and Reef Zone and smaller individuals at the Estuarine zone, was recorded for Abudefduf saxatilis, Anisotremus surinamensis, Lutjanus alexandrei, and Lutjanus jocu. Our findings clearly suggests ecosystem connectivity between mangrove, seagrass and reef biotopes, and highlighted the importance of Mamanguape Mangrove-Reef System as a priority area for conservation and research, whose habitat mosaics should be further studied and protected.