Abstract: Disruption of gene flow among demes after landscape fragmentation can facilitate local adaptation but increase the effect of genetic drift and inbreeding. The joint effects of these conflicting forces on the mean fitness of individuals in a population are unknown. Through simulations, we explored the effect of increased isolation on the evolution of genetic load over the short and long term when fitness depends in part on local adaptation. We ignored genetic effects on demography. We modeled complex genomes, where a subset of the loci were under divergent selection in different localities. When a fraction of the loci were under heterogeneous selection, isolation increased mean fitness in larger demes made up of hundreds of individuals because of improved local adaptation. In smaller demes of tens of individuals, increased isolation improved local adaptation very little and reduced overall fitness. Short-term improvement of mean fitness after fragmentation may not be indicative of the long-term evolution of fitness. Whatever the deme size and potential for local adaptation, migration of one or two individuals per generation minimized the genetic load in general. The slow dynamics of mean fitness following fragmentation suggests that conservation measures should be implemented before the consequences of isolation on the genetic load become of concern.