Food availability, energetic ceilings, and life-history trade-offs have been proposed as potential determinants of offspring number in many animals. We investigated the role of these factors in determining litter size in a free-ranging population of red squirrels (Tamiasciurus hudsonicus). Long-term observational data were used to assess the influence of food availability, while experimental manipulations of litter size permitted evaluation of the importance of energetic ceilings and life-history trade-offs. Among unmanipulated litters, juvenile growth rate and survival, but not litter size, were significantly related to annual food supply. Experimental increases in offspring number were successfully sustained in a high- and a low-food year, but in both years increases in litter sizes were associated with pronounced declines in juvenile growth rates. However, the reduced size of offspring in augmented litters did not fully compensate for the increase in offspring number, so that the total litter mass supported by augmented females was much higher than that of control females. During late lactation, augmented females were characterized by increased daily energy expenditure, but not by significant changes in time budgets, relative to control females. Increases in litter size did not appear to reduce maternal survival, but were associated with declines in offspring survival. Together, these results indicate that food availability and energetic ceilings do not limit litter size in red squirrels directly, but that trade-offs between offspring number and offspring survival may eliminate any advantage of weaning larger-than-normal litters.