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This study was conducted to investigate if the productive performance of Patagonian red octopus (Enteroctopus megalocyathus) is related to the quantitative contents of protein and energy of fresh diets based in marine preys. Six diets with P/E ratios of 35 (100% crab = C100), 41 (100% fish = F100), 44 (25% squid and 75% fish = S25:F75), 46 (50% squid and 50% fish = S50:F50), 48 (75% squid and 25% fish = S75:F25) and 51 (100% squid = S100) g protein MJ−1 during 83 days were evaluated in octopuses weighing 297 ± 120 g. The growth and body biochemistry of the octopuses were not affected by the diets, however, food and lipid intake were affected, with crab diet obtaining the highest intake in both cases. The higher values of dry matter digestibility were achieved in S100 and S50:F50 diets, the highest protein digestibility was obtained with S100 and C100 diets, while the highest energy digestibility was achieved by diet S75:F25 and F100. Feed efficiency varied between the diets and protein/energy ratio alone explained 82.8% of the total variance. Besides, octopus fed F100 and C100 showed the highest body protein deposition. So, although it had no significant differences in growth and survival between the different diets, the feed efficiency and nitrogen deposition changed in relation with the protein/energy ratio of fresh diets. It is discussed that is possible to maintain growth of octopuses and to improve the feed efficiency and protein deposition parameters by optimizing the P/E values of diet.