ABSTRACT: The marine environment is ever-changing, with daily and seasonal variations in factors such as food availability and seawater temperature. These stressors can affect physiological processes in aquatic organisms, resulting in sub-lethal or lethal consequences. This study assessed the effects of food limitation (i.e. fasting) on heat-stress responses in juveniles (~1.3 mm in shell length) of the green-lipped mussel Perna canaliculus. Fasting for up to 24 h did not have a significant effect on oxidative damage (protein carbonyls and lipid hydroperoxide accumulation) or the activity of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase) after exposure to heat stress. However, fasting for 54 h and subsequent heat stress resulted in increased oxidative damage and decreased activity of antioxidant enzymes in juvenile mussels. Gene expression of 70 kDa heat shock protein (hsp70) was only significantly affected by heat shock, not nutritional status. Tissue carbohydrate and protein levels were significantly depleted by 54 h of fasting; as these proximate components represent key energy substrates for bivalves, it is suggested that energy limitation contributes to compromised antioxidant activity and predisposition to oxidative damage.