The acute effects of drinks rich in protein (PRO) versus carbohydrate (CHO) on cardiovascular hemodynamics and reactivity are uncertain. A randomized crossover design was used to compare 400-mL isoenergetic (1.1 MJ) drinks containing whey protein (PRO; 44 g) or carbohydrate (CHO; 57 g) versus 400 mL of water in 14 healthy men. The primary and secondary outcomes were changes in cardiac output, blood pressure, systemic vascular resistance (SVR) and digital volume pulse measured prior to and 30 min following consumption at rest, during 12 min of multi-stage bicycle ergometry, and 15 min postexercise. The mean change (95% confidence interval (CI)) in resting cardiac output at 30 min was greater for CHO than for PRO or water: 0.7 (0.4 to 1.0), 0.1 (–0.2 to 0.40), and 0.0 (–0.3 to 0.3) L/min (P < 0.001), respectively; the higher cardiac output following CHO was accompanied by an increase in stroke volume and a lower SVR. The mean increments (95% CI) in cardiac output during exercise were CHO 4.7 (4.4 to 5.0), PRO 4.9 (4.6 to 5.2), and water 4.6 (4.3 to 4.9) L/min with the difference between PRO versus water being significant (P < 0.025). There were no other statistically significant differences. In summary, a CHO-rich drink increased cardiac output and lowered SVR in the resting state compared with a PRO-rich drink or water but the effect size of changes in these variables did not differ during or after exercise between CHO and PRO. Neither protein nor carbohydrate affected blood pressure reactivity to exercise.