Hypercholesterolemia is a major risk factor for cardiovascular disease (CVD). Interestingly, the consumption of dairy products, namely milk, has been shown to lower cholesterol. The mechanism of action surrounding this observation has been attributed to the protein fraction of milk. While there have been many studies evaluating the effects of dietary protein sources on cholesterol concentrations, few studies have evaluated specific animal protein components and no human clinical studies regarding the effects of animal plasma protein fractions on cholesterol metabolism have been conducted. This study examined the effect of an oral serum bovine immunoglobulin protein fraction (bIg) derived from US Department of Agriculture approved beef (aged < 30 months) on lipid indices in hypercholesterolemic humans. Participants included men and women (aged 25 – 70 years) with mild hypercholesterolemia (5.44-6.99 mmol/L) who were not receiving cholesterol-lowering medication. Treatment consisted of the randomized, double blind, parallel group, placebo-controlled administration of 5 grams (g) bIg daily for 6 weeks (W) in 52 participants (n = 26 each in treatment and control groups). Mean (± SD) baseline treatment and placebo total cholesterol (TC) was 6.33 ± 0.1 mmol/L and 6.16 ± 0.1 mmol/L respectively. A repeated-measures multivariate analysis of covariance (MANCOVA) covaried for change in total energy and alcohol intake, and a Tukey posthoc examination of the data showed that the bIg-treated group demonstrated a significant reduction in TC at 3-week (W) (5.98 ± 0.5 mmol/L; P < 0.05) and 6-week (W) (5.97 ± 0.7 mmol/L; P > 0.05) intervals compared to baseline. The 6W concentration was significantly lower than the placebo group (P < 0.05). Additionally, study findings displayed no significant changes in the placebo group or in any other lipid indexes or markers associated with hepatorenal or cardiovascular health. Consumption of bIg appears to lower major lipid indexes associated with CVD.