Objective: Inflammation plays an important role in atherosclerosis. Elevated C-reactive protein (CRP) levels are associated with a greater risk of cardiovascular disease. Our goal was to study CRP metabolism, and to determine its relationship with lipoprotein metabolism using stable isotope methodology. Material/Methods: Eight subjects with combined hyperlipidemia underwent a 15-h primed-constant infusion with deuterated leucine. CRP was purified from the plasma density fraction greater than 1.21 g/ml by affinity chromatography. Lipoprotein fractions were separated by sequential ultracentrifugation. Isotope enrichment was determined by gas chromatography/mass spectrometry. Results: The subjects had mean LDL-C levels of 147.5 mg/dl and mean CRP levels of 3.4 mg/l. The mean CRP production rate (PR) was 0.050 ± 0.012 mg/kg/day and the mean CRP fractional catabolic rate (FCR) was 0.343 ± 0.056 pools/day (residence time 2.92 days). CRP pool size (PS) was significantly related to production (r = 0.93; p <0.001), but not FCR. CRP PS was also related to body mass index (r = 0.79; p = 0.02). There was a significant association between CRP FCR and TRL apoB-100 FCR (r = 0.74, p = 0.04), as well as between CRP PS and TRL apoB-48 FCR (r = - 0.90, p = 0.002), indicating linkage between CRP and TRL metabolism. Conclusion: The main determinant of plasma CRP levels was CRP production rate. Moreover a significant linkage between CRP metabolism and both TRL apoB-100 and apoB-48 catabolism was noted.