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The seasonal changes in biochemical composition of the edible bivalve Arca noae harvested from a Mediterranean coastal lagoon (Bizerte lagoon, Tunisia) were investigated from October 2013 to September 2014. Potential food sources and nutritional quality indices (NQI) were determined by analyzing the fatty acid profiles of their tissues during an annual reproductive cycle. Results showed that A. noae had moisture (73.8–82%) and protein (24.1–58.6% dry weight) as major components, followed by lipid (10.4–28.8% dry weight) and glycogen (4.05–14.6% dry weight). A. noae accumulated lipid and glycogen for gonadal development during both maturation periods (late autumn/late spring–summer) to be used during spawning periods (winter/late summer–early autumn). However, proteins were mainly used to support reproductive allocation and played an important role on the energetic maintenance. Lipid and glycogen were found to be significantly related to temperature, salinity and chlorophyll a (p