Abstract <p>The fatty acid (FA) composition of the mantle, foot (muscle), and hepatopancreas of the European pearl mussel <i>Margaritifera margaritifera</i> from the Kem River (estuary), the Ukhta River, and the Vozhma River (Republic of Karelia, Russia) was studied for the first time. All tissues of the pearl mussel from the studied rivers were shown to have a higher content of saturated and polyunsaturated FAs compared to monounsaturated ones, which may be due to the post-spawning period. In the hepatopancreas of the pearl mussel, a predominance of polyunsaturated FAs due to the FAs of n-3 family, as well as a higher amount of 16:1(n-7), 18:1(n-7), 18:3(n-3), 20:5(n-3), and 22:6(n-3) FAs and a lower amount of 16:0, 18:0, 18:1(n-9), 20:1(n-11), and 20:4(n-6) FAs compared to the foot and mantle was shown. An important distinctive feature of <i>M. margaritifera</i> is the high amount of 20:1(n-11) FA. Mollusks from the Kem River estuary were distinguished by a higher content of 18:0 and 20:5(n-3) FAs in all the studied tissues and a lower content of 18:1(n-7), 18:2(n-6), and 22:6(n-3) FAs. The obtained data are important for monitoring work to assess the state of pearl mussel populations in different rivers of the European North (in particular, using physiological and biochemical indices).</p>