OBJECTIVE To determine if an echinacea-based dietary supplement (EBS) provided at two different doses (a regular dose (RD), 8,000 mg/day, vs. a double dose (DD), 16,000 mg/day) would increase erythropoietin (EPO) and other blood markers involved in improving aerobic capacity and maximal oxygen consumption (VO2max) in endurance-trained men. Secondly, to determine if any sex differences exist between male and female endurance-trained athletes. METHODS Forty-five endurance athletes completed three visits during a 35-day intervention. Participants were randomized into placebo (PLA; n = 8 men, n = 7 women), RD of EBS (n = 7 men, n = 8 women), or DD of EBS (n = 15 men) for the 35-day intervention period. At baseline, weight, body composition, and VO2max were measured. Blood was drawn to measure EPO, ferritin, red blood cells, white blood cells, hemoglobin, and hematocrit. At the mid-intervention visit, blood was collected. At the post-intervention visit, all measurements from the baseline visit were obtained once again. RESULTS There was a significant increase in VO2max for endurance-trained men in PLA (increase of 2.8 ± 1.5 ml kg(-1) min(-1), p = .01) and RD of EBS (increase of 2.6 ± 1.8 ml kg(-1) min(-1), p = .04), but not in DD of EBS (p = .96). Importantly, there was no difference in the change in VO2max between PLA and RD of EBS. For endurance-trained women, VO2max did not change in either treatment (PLA: -0.7 ± 1.7 ml kg(-1) min(-1), p = .31; RD of EBS: -0.2 ± 2.4 ml kg(-1) min(-1), p = .80). There were no significant changes in any blood parameter across visits for any treatment group. CONCLUSIONS This EBS should not be recommended as a means to improve performance in endurance athletes.