Pomegranate is a rich source of polyphenols. Laboratory studies suggest polyphenols may exert breast cancer preventive effects through modulation of endogenous sex hormone levels. The aim of this study was to determine the effect of pomegranate juice consumption on serum levels of estradiol, estrone, testosterone, androstenedione, and sex hormone binding globulin (SHBG). Sixty-four healthy postmenopausal women were randomly assigned to drink 8 ounces of either 100% commercial pomegranate juice (intervention) or apple juice (control) for 3 weeks. Overall, women in the intervention group did not experience any significant decline in serum sex hormones or SHBG compared to women in the control group. In subgroup analyses restricted to 38 normal weight women, women in the intervention group compared to control group had a significant decline in estrone (pg/mL) and testosterone levels (pg/mL): pomegranate: -61.6 [95% confidence interval (CI): -175.8 to 52.6), apple: 1.1 (95% CI: -5.4 to 7.7), P = 0.05, and pomegranate: -289.1 (95% CI: -630.7 to 52.5), apple: 79.6 (95% CI: -77.8 to 236.9), P = 0.03, respectively. Because of several study limitations, results should be considered preliminary. Additional larger trials would be needed to determine effects in normal versus overweight/obese women.