PURPOSE: The aims of the present study were to test the hypothesis that caffeine increases maximal oxygen uptake (V˙O2max) and to characterize the physiological mechanisms underpinning improved high-intensity endurance capacity. METHODS: Twenty-three elite endurance-trained male athletes were tested twice with and twice without caffeine (four tests) in a randomized, double-blinded, and placebo-controlled study with crossover design. Caffeine (4.5 mg·kg-1) or placebo was consumed 45 min before standardized warm-up. Time to exhaustion during an incremental test (running 10.5° incline, start speed 10.0 km·h-1, and 0.5 km·h-1 increase in speed every 30 s) determined performance. Oxygen uptake was measured continuously to determine V˙O2max and O2 deficit was calculated. RESULTS: Caffeine increased time to exhaustion from 355 ± 41 to 375 ± 41 s (Δ19.4 ± 16.5 s; P < 0.001). Importantly, caffeine increased V˙O2max from 75.8 ± 5.6 to 76.7 ± 6.0 mL·kg-1·min-1 (Δ 0.9 ± 1.7 mL·kg-1·min-1; P < 0.003). Caffeine increased maximal heart rate (HRpeak) and ventilation (VEpeak). Caffeine increased O2 deficit from 63.1 ± 18.2 to 69.5 ± 17.5 mL·kg-1 (P < 0.02) and blood lactate compared with placebo. The increase in time to exhaustion after caffeine ingestion was reduced to 11.7 s after adjustment for the increase in V˙O2max. Caffeine did not significantly increase V˙O2max after adjustment for VEpeak and HRpeak. Adjustment for O2 deficit and lactate explained 6.2 s of the caffeine-induced increase in time to exhaustion. The increase in V˙O2max, VE, HR, O2 deficit, and lactate explained 63% of the increased performance after caffeine intake. CONCLUSION: Caffeine increased V˙O2max in elite athletes, which contributed to improvement in high-intensity endurance performance. Increases in O2 deficit and lactate also contributed to the caffeine-induced improvement in endurance performance.