Defatted microalgal biomass derived from biorefinery can be potential feed ingredients for carnivorous fish. The present study investigated the growth, feed intake:gain and health parameters in Atlantic salmon fed for 84 days with defatted Nannochloropsis oceania as a fishmeal replacer. Fish fed feeds containing the algal biomass (at 10 and 20% inclusion, alga groups) were compared with groups that consumed alga-devoid feeds (control group). The fish that received 20% alga tended to have reduced weight gain and specific growth rate. Condition factor, feed conversion ratio and feed intake of this fish group were significantly different when compared with the control group. Hepatosomatic and viscerosomatic indices, whole body and fillet proximate composition were not affected by the dietary treatments. Digestibility of dry matter, protein, lipid, ash and energy, as well as retention of lipid and energy of the fish that received feed with 20% alga meal were also significantly different from those of the control group. Serum superoxide dismutase activity of the 10% alga-fed fish was significantly higher compared with the control fish. Although alga feeding did not cause any distal intestinal inflammation, the intestinal proteins that were altered upon feeding 20% algal meal might be pointing to systemic physiological disturbances. In conclusion, feeds with 20% alga had a negative effect on feed intake, FCR, lipid and energy retention and health of the fish. The defatted Nannochloropsis oceania can be used at modest inclusion levels, around 10%, without negative effects on the performance of Atlantic salmon.