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Arthrospira platensis is an edible cyanobacterium with high nutritional value. Even though A. platensis is not a marine species, it can be adapted to higher salinities, a strategy that could allow mass cultivation using brackish or saline water. In this work A. platensis was long-term adapted at different salinities (5–60 g/L NaCl added as natural sea salt) to evaluate the growth and biochemical composition of the biomass produced. Biomass production was enhanced in salinity up to 40 g/L NaCl, while at 60 g/L NaCl biomass production slightly decreased. However, it displayed higher values compared to the conventional Zarrouk growth medium. By increasing the salinity, carbohydrate content increases, while proteins, phycocyanin, carotenoids, and total phenolics decreased. Biomass content in lipids, and chlorophyll along with the antioxidant capacity of extracts, was not significantly affected. A. platensis tended to increase the unsaturated fatty acids, while amino acid composition was not significantly affected by the increased salinity. However, in vitro protein digestibility was negatively affected when salinity was above 20 g/L NaCl. It was macroscopically observed that trichomes were longer at higher salinities, and especially at 40 g/L NaCl. The results suggest that A. platensis when acclimated in long-term can be grown successfully at various salinities.