The contents of the bioactive compounds in the pummelo-grapefruit hybrid juice named Israeli Jaffa Sweetie and their influence on humans suffering from hypercholesterolemia were studied. It was found that Sweetie juice has a high content of bioactive compounds and a high antioxidant potential. Then 72 hypercholesterolemic patients, ages 43-71 years, after coronary bypass surgery recruited from the Institute pool of volunteers, were randomly divided into two experimental (EG1 and EG2) groups and one control (CG) group, each comprising 24 patients. The diets of EG1 and EG2 patients were daily supplemented with 100 or 200 mL of fresh Sweetie juice, respectively. Before and after diet consumption serum lipid levels, albumin and fibrinogen fractions, and their antioxidant capacities were determined. After 30 consecutive days of Sweetie juice supplemented diets, improvements in serum lipids levels were found in EG1 and EG2 versus CG: (a) total cholesterol, 7.34 versus 8.02 mmol/L, -9.5%, and 6.73 versus 8.02 mmol/L, -16.1%, respectively; (b) low-density lipoprotein cholesterol, 5.63 versus 6.37 mmol/L, -11.6%, and 5.03 versus 6.37 mmol/L, -21.0%, respectively; (c) total glycerides, 2.01 versus 2.27 mmol/L, -11.5%, and 1.71 versus 2.27 mmol/L, -24.7%, respectively. Serum albumin concentration was increased but not significantly in EG1 and EG2 versus CG: 47.5 versus 44.5 g/L, +6.7%, and 47.9 versus 44.5 g/L, +7.6%, respectively. A significant increase in the serum, albumin, and fibrinogen antioxidant capacities in EG2 and to a lesser degree in EG1 was observed. No changes in the CG were found. In conclusion, fresh Sweetie juice contains high quantities of bioactive compounds and has a high antioxidant potential. Diet supplemented with this juice positively influences serum lipid, albumin, and fibrinogen levels and their antioxidant capacities. Addition of fresh Sweetie juice to generally accepted diets may be beneficial for hypercholesterolemic patients.