The present work is the first study of Mediterranean scallop (Pecten jacobaeus) biochemical properties, antioxidant defenses, and free radical scavengers during the yearly seasons in the Northern Adriatic, off Istria. Scallop nutrient reserves (glucose, triglyceride, and cholesterol) in four tissues under examination were positively correlated and were predominant in digestive gland and gonad. The muscle energy maxima were in correlation with the maximum fall gonosomatic index (GSI), when diatoms and coccolithophorids thrive. The decrease of GSI in summer might be related to the spawning or resorption of gametes. Summer also revealed elevated levels of glucose in gonad and digestive gland, while muscle glucose and cholesterol significantly varied in spring vs. winter samples. In relation to the diatom seasonal abundance, carotenoids, namely astaxanthin peaks were found in digestive gland, which, being stimulators of calcium transport over cell membranes, could have contributed to the high digestive gland levels of calcium in winter. In winter, total antioxidative status (TAS) of scallop tissues was 3-fold higher than in other seasons, particularly in digestive gland, having a significant correlation with magnesium, a regulatory tool in oxidative processes. The winter maxima of TAS and thiobarbituric acid reactive substances TBARS in relation to summer maxima of glutathione peroxidase and superoxide dismutase in digestive glands indicate to a decrease in antioxidant defense during cold months, and are related to the accumulation of lipid peroxidation products (such as malondialdehyde) in digestive gland of scallops. Although the increased susceptibility to oxidative stress could be attributed to winter temperature, other factors such as the gonad maturation, availability of food supply, and salinity might counteract that effect. The seawater alterations of salinity, temperature and water quality are in relation to the river Po influx, which is very likely to influence the physiological and biochemical responses of scallops in the Northern Adriatic.