Long-chain polyunsaturated fatty acids (LC n-3 PUFA), particularly docosahexaenoic acid (DHA), are essential for cell membrane structure and function, impacting overall fish performance. These molecules are produced primarily by phytoplankton and transferred up the trophic chain; however, due to climate change, reduced DHA production by primary producers is anticipated, potentially decreasing DHA availability for fish. This study aimed to evaluate the effects of dietary DHA limitation on i) growth, swimming performance, and metabolic rates, and ii) the activation of biosynthetic pathways for DHA compensation at the molecular level, by measuring gene expression involved in DHA synthesis. We conditioned wild-caught European sea bass juveniles for five months on either a DHA-depleted or control diet. Dietary DHA limitation led to selective retention or synthesis in fish tissues (liver, brain, and white muscle), up-regulation of DHA biosynthetic pathways, and reduced growth without fully compensating for DHA deficiency in tissues. Fish fed the low DHA diet showed increased biosynthetic activity, suggesting this pathway may be energetically costly, as high tissue DHA levels correlated with reduced growth. Alternatively, the lower tissue DHA levels in these fish might directly cause slower growth. However, metabolic rates and swimming performance were not affected by dietary DHA levels. Significant inter-individual variability was observed across all variables, highlighting underlying trade-offs in coping with DHA limitation. This work provides insight into the physiological consequences of dietary DHA reduction due to global change and the molecular mechanisms fish employ to mitigate its effects.