Obesity in the United States continues to worsen. Anthocyanin-rich fruits and vegetables provide a pragmatic dietary approach to slow its metabolic complications. Given American diet patterns, foods with high anthocyanin content could address dose-response challenges. The study objective was to determine the effect of 100% elderberry juice on measures of indirect calorimetry (IC) and insulin sensitivity/glucose tolerance in a placebo-controlled, randomized, crossover pilot study. Overweight and obese adults were randomized to a 5-week study which included 2 1-week periods of twice-daily elderberry juice (EBJ) or sugar-matched placebo consumption separated by a 3-week washout period. Following each 1-week test period, IC and insulin sensitivity/glucose tolerance was measured with a 3 h meal tolerance test (MTT). Treatment differences were tested with linear mixed modeling. A total of 22 prospective study volunteers (18 F/4 M) attended recruitment meetings, and 9 were analyzed for treatment differences. EBJ was well tolerated and compliance was 99.6%. A total of 6 IC measures (intervals) were created, which coincided with 10–20 min gaseous samplings in-between MTT blood samplings. Average CHO oxidation was significantly higher during the MTT after 1-week EBJ consumption (3.38 vs. 2.88 g per interval, EBJ vs. placebo,p= 0.0113). Conversely, average fat oxidation was significantly higher during the MTT after 1-week placebo consumption (1.17 vs. 1.47 g per interval, EBJ vs. placebo,p= 0.0189). This was in-line with a significantly lower average respiratory quotient after placebo treatment (0.87 vs. 0.84, EBJ vs. placebo,p= 0.0114). Energy expenditure was not different. There was no difference in serum glucose or insulin response between treatments. This pilot study of free-living volunteers describes significant change in IC but not insulin sensitivity with an EBJ intervention. Controlled feeding and increased sample size will help determine the utility of EBJ on these outcomes.