Aquatic ecosystems can exhibit seasonal variation in resource availability and animals have evolved to cope with the associated caloric restriction. During winter in the NW Mediterranean Sea, the European sardine Sardina pilchardus naturally experiences caloric restriction due to a decrease in diversity and quantity of plankton. Ongoing global warming has, however, had deleterious effects on plankton communities such that food shortages may occur throughout the year, especially under warm conditions in the summer. We investigated the interactive effects of temperature and food availability on sardine metabolism, by continuously monitoring whole-animal respiration of groups of control (fed) and food-deprived sardines over a 60-day experiment in winter (12°C) or summer (20°C) conditions under natural photoperiod. In addition, we measured mitochondrial respiration of red muscle fibres, biometric variables and energy reserves, of individuals sampled at 30 and 60 days. This revealed that winter food deprivation elicits energy saving mechanisms at whole animal and cellular levels by maintaining a low metabolism to preserve energy reserves, allowing high survival. By contrast, despite energy saving mechanisms at the mitochondrial level, whole animal metabolic rate was high during food deprivation in summer, causing increased consumption of energy reserves at the muscular level and high mortality after 60 days. Furthermore, a 5-day refeeding did not improve survival and mortalities actually continued, suggesting that long-term food deprivation at high temperatures caused profound stress in sardines that potentially impaired nutrient absorption.