Microalgae companies increasingly seek markets for defatted biomass that is left over after extracting omega-3 rich oil for human nutraceuticals and crude oil for fuels. Such a protein-rich co-product is a promising alternative to unsustainably sourced fishmeal in aquaculture diets. We report the first evaluation of co-product of the marine microalga Nannochloropsis oculata (N. oculata co-product) for replacing fishmeal in diets of Nile tilapia, a globally important aquaculture species. We conducted a nutrient digestibility experiment with N. oculata dried whole cells and N. oculata co-product, followed by an 84-day nutritional feeding experiment with N. oculata co-product. N. oculata co-product, more nutrient-dense than whole cells, had the highest digestibility for lysine, an essential amino acid that is often deficient in terrestrial crop meals; and for 20:5 n-3 EPA, making it a good option for EPA supplementation in tilapia feed. N. oculata co-product, despite containing higher amounts of protein than whole cells, had significantly lower digestibility for crude protein than whole cells. Apparent digestibility coefficients (ADC) of methionine were significantly lower in N. oculata co-product than in whole cells. The nutritional feeding experiment compared diets with N. oculata co-product that replaced fishmeal as follows: 0% replacement in reference diet (fishmeal as 7% of total diet) and test diets with 33%, 66% and 100% replacement of fishmeal (3%, 5.5%, and 8% of total diet, respectively). Results showed the 33% replacement diet yielded fish growth, feed conversion, and survival similar to the reference diet. Reduced digestibility and growth at greater N. oculata co-product inclusion levels may have been due to higher levels of anti-nutrients in co-product than whole cells. All diets yielded a n3:n6 ratio of tilapia fillet that is favorable for human consumption. Depositions of macro minerals and several trace elements in the fillet were not significantly different across diets. Thus, N. oculata co-product, when replacing 33% of fishmeal in tilapia feed, led to fish performance and flesh composition comparable to that of fish fed the reference diet, but its nutrient digestibility needs to be improved to achieve higher replacement levels.