To investigate the potential benefits of the catadromous thinlip grey mullet (Chelon ramada Risso, 1827) migration to freshwater, the total lipid content and fatty acid (FA) profile of female’s muscle and gonads caught in both the estuary and river were analyzed. The freshwater contingent presented a higher body condition, greater muscle gross energy, and larger gonads with higher lipid reserves. These animals showed a muscle profile rich in C16:1n-7 and lower LC-PUFA that contrast with the higher relative amount of C18:1n-9, n-3 FA, and unsaturated LC-PUFA, such as C18 and C20 FA found in the estuarine contingent. The gonads of both contingents showed a constant and high relative amount of polyunsaturated FAs (PUFA, 37%). However, in terms of essential fatty acids (EFAs), the estuarine contingent had a higher relative amount of C18:2n-6, C20:4n-6, C20:5n-3, and C22:6n-3. On the other hand, the freshwater contingent showed a higher relative amount of n-3 FA precursors, namely C18:3n-3, and a still low relative amount of C22:6n-3. This suggests a mismatch between the metabolic omega-3 pathway and the physiological maturity stages, similar to a phenomenon of dormancy. In this sense, not all these individuals may reproduce annually, and the later stages of gonad development will require supplementary energy derived from feeding at the estuary. Thus, freshwater migration may promote a reproductive strategy enabling adults to take advantage of the warm and food-rich summer/autumn period, adjust spawning and juvenile appearance, and reduce the population’s exposure to habitat changes and/or stochastic events.