The purpose of this study was to investigate the influence of an energy drink (ED) on cycling performance and immune-related variables. Eleven trained male cyclists (33.4 ± 8.9 years; 81 ± 7.6 kg; maximal VO2, 52 ± 3.4 ml·kg(-1)·min(-1)) consumed 500 ml of (a) ED (2.0 g taurine, 1.2 g glucuronolactone, 160 mg caffeine, 56 g carbohydrate [CHO], and B vitamins), (b) cola matched for caffeine and CHO (CC), or (c) flavored placebo (PL: sparking water and flavoring) 50 minutes before racing in a randomized, crossover design. Performance was measured as time to complete (TTC) a 25-mile simulated road race. Blood was collected at baseline, 30 minutes after drink consumption, during exercise at miles 5 (M5), 15 (M15), and immediately (POEX) and 30 minutes (30minPO) after exercise. TTC was not different (p > 0.05) among trials (ED, 68.6 ± 2.7; CC, 68.9 ± 3.8; PL, 69.6 ± 3.8 minutes). Consumption of CC and ED elicited a mild hypoglycemia elicited a mild hypoglycemia during cycling. POEX interleukin-6 (IL-6) was greatest after ED, whereas CC IL-6 was greater than PL (10.2 ± 1.6, 6.7 ± 0.6, and 4.8 ± 0.7 pg·ml(-1), respectively; p < 0.001). Cycling increased leukocyte number in all conditions with ED leukocyte number greater than that of PL at M15 (9.8 ± 0.6, 8.5 ± 0.3 × 10(6) cells·mL(-1)). Energy drink induced an earlier recruitment of monocytes to the blood stream than CC. Mean fat oxidation was greater in PL compared with CC (0.43 ± 0.06 and 0.28 ± 0.04 g·min(-1); p = 0.033) but did not differ between ED (0.32 ± 0.06) and PL. Lactate was higher in ED compared with CC and PL at M5 and M15 (p = 0.003), but there was no significant influence of either ED or CC on performance. Carbohydrate and caffeine consumption before endurance cycling significantly increased the IL-6 release and leukocytosis, and the additional ingredients in ED seem to have further augmented these responses.