ABSTRACT: Old skeletal muscle exhibits decreased anabolic sensitivity, eventually contributing to muscle wasting. Besides anabolism, also muscle inflammation and catabolism are critical players in regulating the old skeletal muscle's sensitivity. Omega-3 fatty acids (?-3) are an interesting candidate to reverse anabolic insensitivity via anabolic actions. Yet, it remains unknown whether ?-3 also attenuates muscle inflammation and catabolism. The present study investigates the effect of ?-3 supplementation on muscle inflammation and metabolism (anabolism/catabolism) upon resistance exercise (RE). Twenty-three older adults (65-84 years; 8?) were randomized to receive ?-3 (~3 g/d) or corn oil (placebo [PLAC]) and engaged in a 12-week RE program (3×/wk). Before and after intervention, muscle volume, strength, and systemic inflammation were assessed, and muscle biopsies were analyzed for markers of anabolism, catabolism, and inflammation. Isometric knee-extensor strength increased in ?-3 (+12.2%), but not in PLAC (-1.4%; pinteraction = .015), whereas leg press strength improved in both conditions (+27.1%; ptime < .001). RE, but not ?-3, decreased inflammatory (p65NF-?B) and catabolic (FOXO1, LC3b) markers, and improved muscle quality. Yet, muscle volume remained unaffected by RE and ?-3. Accordingly, muscle anabolism (mTORC1) and plasma C-reactive protein remained unchanged by RE and ?-3, whereas serum IL-6 tended to decrease in ?-3 (pinteraction = .07). These results show that, despite no changes in muscle volume, RE-induced gains in isometric strength can be further enhanced by ?-3. However, ?-3 did not improve RE-induced beneficial catabolic or inflammatory adaptations. Irrespective of muscle volume, gains in strength (primary criterion for sarcopenia) might be explained by changes in muscle quality due to muscle inflammatory or catabolic signaling.