Plantation clearcuts represent an important habitat for many open-area wildlife species – including conservation-concern species – in landscapes dominated by industrial forests. However, due to the ephemeral nature of clearcuts, species using this type of environment face a “shifting mosaic” in which their ability to successfully relocate to another habitat patch may play a crucial role in the species’ persistence in the landscape. Although several studies have shown a positive effect of patch size on the persistence of open-habitat species, forest clearcutting represents a special case in which, on average, larger patches also tend to be more isolated from each other, likely creating a trade-off between area and isolation effects. We developed an individual-based spatially-explicit model to test the effect of clearcut size (a critical management variable in plantation forestry) on the persistence of generic early-successional wildlife species in a landscape dominated by forest plantations. We simulated a landscape covered with a plantation harvested regularly over a 25-year rotation and different versions of a wildlife population whose habitat was constituted only by 1–4 year-old patches. We observed that when the species could perceive the attributes of the neighboring pixels persistence time was higher at intermediate clearcut sizes agreeing with our prediction. Also, species with a high dispersal capacity were less limited by connectivity and reached their maximum persistence at higher clearcut sizes. Results also showed a positive effect of habitat lifetime on persistence. Our results suggest large clearcuts may be incompatible with the conservation of many early-successional vertebrates that have limited dispersal capacity, unless additional conservation measures, such as the use of corridors or special spatial arrangement of clearcuts, are taken to overcome the lack of connectivity.