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 owing to a decrease in the diversity and quantity of plankton. However, ongoing global warming has 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 levels of 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 re-feeding did not improve survival, and mortalities continued, suggesting that long-term food deprivation at high temperatures causes profound stress in sardines that potentially impairs nutrient absorption.