Background Evidence regarding the effects of the omega-3 (ɷ-3) PUFAs (n–3 PUFAs) DHA and EPA on cognition is lacking. Objectives We investigated whether supplementation with oils rich in EPA or DHA improves cognition, prefrontal cortex (PFC) hemoglobin (Hb) oxygenation, and memory consolidation. Methods Healthy adults (n = 310; age range: 25–49 y) completed a 26-wk randomized controlled trial in which they consumed either 900 mg DHA/d and 270 mg EPA/d (DHA-rich oil), 360 mg DHA/d and 900 mg EPA/d (EPA-rich oil), or 3000 mg/d refined olive oil (placebo). Cognitive performance and memory consolidation were assessed via computerized cognitive test battery. PFC Hb oxygenation was measured using near infrared spectroscopy (NIRS). Results Both global accuracy and speed improved with EPA-rich oil compared with placebo and DHA-rich oil [EPA vs. placebo accuracy: estimated marginal mean (EMM) = 0.17 (95% CI: 0.09, 0.24) vs. EMM = 0.03 (95% CI = −0.04, 0.11); P = 0.044; EPA vs. placebo speed: EMM = −0.15 (95% CI: −0.22, −0.07) vs. EMM = 0.03 (95% CI: −0.05, 0.10); P = 0.003]. Accuracy of memory was improved with EPA compared with DHA [EMM = 0.66 (95% CI: 0.26, 1.06) vs. EMM = −0.08 (95% CI: −0.49, 0.33); P = 0.034]. Both EPA- and DHA-rich oils showed trends towards reduced PFC oxygenated Hb (oxy-Hb) compared with placebo [placebo: EMM = 27.36 µM (95% CI: 25.73, 28.98); DHA: EMM = 24.62 µM (95% CI: 22.75, 26.48); P = 0.060; EPA: EMM = 24.97 µM (95% CI: 23.35, 26.59); P = 0.082]. Conclusions EPA supplementation improved global cognitive function and was superior to the oil enriched with DHA. Interpreted within a neural efficiency framework, reduced PFC oxygenated Hb suggests that n–3 PUFAs may be associated with increased efficiency. These trials were registered in the clinical trials registry (https://clinicaltrials.gov/) as NCT03158545, NCT03592251, NCT02763514.