The European spiny lobster is a species of great commercial value, yet a limited scientific knowledge exists on its biology, ecology, and physiology, especially for the stocks from east Mediterranean waters. The northern brown shrimp, a non-indigenous established species, is commercially exploited in regions of the Mediterranean Sea. Both species’ proximate composition and fatty acid profile were assessed for the first time in the Mediterranean region, exhibiting an overall significant statistical difference. Protein, fat, and energy contents were significantly higher in the northern brown shrimp, whereas moisture and ash contents were significantly higher in the European spiny lobster. The proximate composition for both species was well within the reported range for other lobster and prawn species in the Mediterranean Sea.