It is unclear whether the rate of weight loss, independent of magnitude, affects whole body protein metabolism and the synthesis and plasma concentrations of specific hepatic secretory proteins. We examined (i) whether lean men losing weight rapidly (starvation) show greater changes in whole body protein kinetics, synthesis and circulating concentrations of selected hepatic secretory proteins than those losing the same amount of weight more slowly (very low energy diet (VLED) (ii) whether plasma concentrations and synthetic rates of these proteins are related. Whole body protein kinetics was measured using [1-¹³C] leucine in 11 lean men (6 starvation, 5 VLED). Fractional and absolute synthetic rates of HDL-apoA1, retinol binding protein (RBP), transthyretin (TTR), alpha-1 antitrypsin (-1-AT) and transferrin (TR) were measured using a prime-constant intravenous infusion of [¹³C₂] glycine. Compared to VLED group, the starvation group showed greater increases (at a 5% weight loss) in whole body protein oxidation (p<0.05); fractional synthetic rates of HDL-apoA1 (25.3% versus -1.52 %; p = 0.003) and RBP (30.6% versus 7.1%; p = 0.007); absolute synthetic rates of HDL-apoA1 (7.1 versus -3.8 mg/kg/day; p=0.003) and -1-AT (17.8 versus 3.6 mg/kg/day; p=0.02); and plasma concentration of -1-AT (p=0.025). Relationships between synthetic rates and plasma concentrations varied between the secreted proteins. It is concluded that synthetic rates of hepatic secreted proteins in lean men are more closely related to the rate than the magnitude of weight loss. Changes in concentration of these secreted proteins can occur independently of changes in synthetic rates and vice versa.