The aim of this work was to investigate the seasonal variability in the biochemical composition in both sexes of Loligo forbesi, (Streenstrup 1856) in two locations in Egypt: the Mediterranean Sea off the coasts of Alexandria and north of the Gulf of Suez. The study is also aimed to document for the first time the fatty acids composition in both sexes in each location. There was a significant difference in the seasonal variations of total protein (P = 0.0001), total lipids (P = 0.036) and total carbohydrates (P = 0.009). Also, there was a significant difference in total lipids (P = 0.008) between sexes. Total lipids and protein declined from spring to summer and then increased in fall before they decrease again in the winter in males and females. Meanwhile, the concentration of total carbohydrates in females decreased from spring to fall then increased slightly in winter. There was a negative correlation between Gonado Somatic Index and Nidamental gland Somatic Index and each of total protein and lipids in different sexes (P = 0.01), which was not the case with total carbohydrates (P = 0.1). Seasonal fluctuations in biochemical content were attributable to the reproductive state of the animal. Although there was no significant difference in either total saturated lipids or total unsaturated lipids among the two sexes or between the two locations (P > 0.05), variations were observed in some fatty acids. The most predominant saturated fatty acid was palmitic acid (C16:0), comprising 68% to 73% for both sexes and locations. Most of the monounsaturated content was present as Cis-Pentadecanoic (C15:1) and palmiboleic (C16:1). Omega 3-poly-unsaturated fatty acids, which include linolenic, EPA, and DHA comprised ∼80% of total polyunsaturated fatty acids.