The objective of the present study was to determine the combined effects of cod protein and fish oil on the modulation of triglyceride metabolism in rats, and to evaluate their potential mechanisms of action. Plasma and hepatic lipid concentrations, triglyceride (TG) secretion rates and postheparin plasma lipoprotein lipase (LPL) activity were determined in rats fed for 28 d diets varying in both protein (200 g/kg) and lipid (140 g/kg) sources: 1) casein-menhaden oil, 2) casein-beef tallow, 3) cod protein-menhaden oil or 4) cod protein-beef tallow. Menhaden oil feeding diminished hepatic TG concentrations (P = 0.02), hepatic TG secretion rates (P = 0.003) and triglyceridemia (P = 0.02) compared with beef tallow. Hepatic TG concentrations (P = 0.05) and TG secretion rates (P = 0.04) were reduced in rats fed cod protein compared with those fed casein. The protein source did not exert an independent effect on triglyceridemia, whereas the combination of cod protein and menhaden oil resulted in 50% lower plasma TG compared with the casein-beef tallow mixture, whereas the combination of menhaden oil and casein did not significantly decrease triglyceridemia compared with casein-beef tallow. Menhaden oil (P = 0.005) and cod protein (P = 0.03) also lowered plasma cholesterol concentrations in comparison with beef tallow and casein, respectively. This was associated with a reduction in hepatic cholesterol concentrations when rats fed cod protein were compared with those fed casein (P = 0.006). No diet effect was observed on postheparin plasma LPL activity, but the activity of hepatic triglyceride lipase was reduced in rats fed menhaden oil compared with those fed beef tallow. These findings show that both cod protein and menhaden oil exert independent and beneficial effects on lipid metabolism in rats.