Female white-footed mice Peromyscus leucopus (Rafinesque, 1818) and their dependent offspring were monitored in nest boxes to determine the extent and causes of nest mortality. The mortality of dependent young was high (561 of 838; 66%) and variable among years. Most mortality involved the loss of entire litters (112 of 183 litters; 61%), with half of these losses attributed to the death of lactating females before the young were weaned (59 of 112 litters; 53%). Most mortality was from unknown causes, although infanticide, energetic constraints and predation were identified in a small number of cases. Predation is likely the major source of mortality in this population.