Although gilthead sea bream have been cultured successfully for the last two decades they are particularly sensitive to low temperature. Especially in the northern Mediterranean area, cold affects fish health and decreases fish-farm production, and may even cause mortality through what is known as ‘Winter Disease’ or ‘Winter Syndrome’. This paper reviews the diagnosis and physiological effects of this disease, focusing on recent studies of cold-induced alterations in gilthead sea bream physiology. ‘Winter Syndrome’ is characterised by multi-organ dysfunction entailing hyposensitivity, erratic swimming, pale and friable livers, necrotic muscles, atrophy of the exocrine pancreas, and distended digestive tract. Its complex aetiology involves several factors such as thermal stress, metabolic depression, immune suppression, and occasional opportunistic pathogens. Low temperatures may be the initial cause of all these factors, except pathogen action. Indoor studies have demonstrated that a drop in temperature causes cold-induced fasting, thermal stress and metabolic depression. These immediate effects are related to an ionic imbalance caused by malfunctions of the gills and digestive system. They are also related to a fatty liver, which appeared steatotic and affected hepatic metabolism and blood composition. The result is a lower immune capacity and fish that are more susceptible to infection. There is no significant thermal compensation under cold conditions and in this situation any additional stress factors can cause fish to suffer metabolic collapse. This study reviews the physiological and zootechnical origins of the disease and, where possible, recommends ways of improving culture conditions during pre-cold, cold and recovery periods.