The Lake St Lucia Estuarine System, South Africa, has been under pressure due to recent drought conditions, which led to extreme low lake levels, hypersaline conditions and closure of the mouth. The estuary mouth closed in June 2002 and has remained so for more than two-and-a-half years. A lack of information on biotic responses during extended closed-mouth conditions prompted a study to ascertain the current status of the fish fauna in the system. Fish were sampled with seine and gill-nets at six sites spread throughout the system. At the time of sampling in December 2004, the system had become partitioned into four isolated compartments. A total of 4 475 fish comprising 30 species were recorded during the survey. The CPUEs were generally low, except for those of Oreochromis mossambicus, Liza dumerili and Ambassis ambassis. The freshwater cichlid O. mossambicus made up 45% of the total catch. The species composition in each of the four compartments of the system were very different. Historical data indicated a loss of about 40% of the commonly-occurring species from the lake since mouth closure, reflecting a substantial change in species composition from that which occurs under 'normal' conditions. It is expected that the decline in the number of species and the abundance of remaining taxa will continue if drought conditions persist and the mouth remains closed.