The populations of sockeye salmon Oncorhynchus nerka of the south-central coast of British Columbia are in decline. To assist in recovery planning, we determined the population structure of sockeye salmon in the region by assaying the genetic variability of 10 microsatellite DNA loci in samples of sockeye salmon from 22 sites associated with 15 rearing lakes. Samples of sockeye salmon from the watersheds with the largest historical runs in the region were studied. Special emphasis was given to investigating genetic divergence among sockeye salmon spawning in seven rivers of the Owikeno Lake watershed, which once supported the largest sockeye salmon run in south-central British Columbia. Across the region, a mosaic of genetic divergence was evident. Reproductive isolation among watersheds was pronounced in all but one case, making transfer of fish between watersheds inadvisable. Genetic stock identification simulations demonstrated that fish from different watersheds could be accurately distinguished — which will allow for identification of threatened stocks in coastal mixed-stock fishery samples. Within the Owikeno Lake watershed we found little evidence of persistent genetic structure, which precludes the use of genetic stock identification to estimate escapements to its glacially turbid tributaries. Lack of persistent structure supports managing the majority of Owikeno Lake sockeye salmon as a single population.