Protein-energy malnutrition is associated with a decrease in immunity and an increase in infectious disease. Both of these effects are exacerbated in aging. Conversely, energy restriction (ER) without malnutrition extends the lifespan in animals and retards the age-related decline in various parameters of immune function. Recent evidence suggests, however, that aged ER mice exhibit an increased mortality in response to primary influenza infection compared with age-matched controls. Underweight may contribute to this outcome due to an inability to meet the energy demands associated with the immune response to primary viral infection. The energetic costs of immune responsiveness must be considered in the undernourished aging population and emerging studies of ER in humans.